Influenza Pathogenesis and Control - Volume II pp 399-421

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 386)

Memory CD4 T Cells in Influenza

Abstract

Influenza A virus is a significant cause of morbidity and mortality worldwide, particularly among young children and the elderly. Current vaccines induce neutralizing antibody responses directed toward highly variable viral surface proteins, resulting in limited heterosubtypic protection to new viral serotypes. By contrast, memory CD4 T cells recognize conserved viral proteins and are cross-reactive to multiple influenza strains. In humans, virus-specific memory CD4 T cells were found to be the protective correlate in human influenza challenge studies, suggesting their key role in protective immunity. In mouse models, memory CD4 T cells can mediate protective responses to secondary influenza infection independent of B cells or CD8 T cells, and can influence innate immune responses. Importantly, a newly defined, tissue-resident CD4 memory population has been demonstrated to be retained in lung tissue and promote optimal protective responses to an influenza infection. Here, we review the current state of results regarding the generation of memory CD4 T cells following primary influenza infection, mechanisms for their enhanced efficacy in protection from secondary challenge including their phenotype, localization, and function in the context of both mouse models and human infection. We also discuss the generation of memory CD4 T cells in response to influenza vaccines and its future implications for vaccinology.

References

  1. Ahmadzadeh M, Farber DL (2002) Functional plasticity of an antigen-specific memory CD4 T cell population. Proc Natl Acad Sci U S A 99(18):11802–11807PubMedCentralPubMedCrossRefGoogle Scholar
  2. Allan W, Tabi Z, Cleary A, Doherty PC (1990) Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol 144(10):3980–3986PubMedGoogle Scholar
  3. Appay V, Zaunders JJ, Papagno L, Sutton J, Jaramillo A, Waters A, Easterbrook P, Grey P, Smith D, McMichael AJ, Cooper DA, Rowland-Jones SL, Kelleher AD (2002) Characterization of CD4(+) CTLs ex vivo. J Immunol 168(11):5954–5958PubMedCrossRefGoogle Scholar
  4. Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, Kemble G, Connor EM (2007) Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 356(7):685–696. doi:10.1056/NEJMoa065368 PubMedCrossRefGoogle Scholar
  5. Belz GT, Wodarz D, Diaz G, Nowak MA, Doherty PC (2002) Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J Virol 76(23):12388–12393PubMedCentralPubMedCrossRefGoogle Scholar
  6. Bentebibel SE, Lopez S, Obermoser G, Schmitt N, Mueller C, Harrod C, Flano E, Mejias A, Albrecht RA, Blankenship D, Xu H, Pascual V, Banchereau J, Garcia-Sastre A, Palucka AK, Ramilo O, Ueno H (2013) Induction of ICOS+CXCR3+CXCR5+TH cells correlates with antibody responses to influenza vaccination. Sci Transl Med 5(176):176ra132. doi:10.1126/scitranslmed.3005191
  7. Bingaman AW, Patke DS, Mane VR, Ahmadzadeh M, Ndejembi M, Bartlett ST, Farber DL (2005) Novel phenotypes and migratory properties distinguish memory CD4 T cell subsets in lymphoid and lung tissue. Eur J Immunol 35:3173–3186PubMedCrossRefGoogle Scholar
  8. Bot A, Bot S, Bona CA (1998) Protective role of gamma interferon during the recall response to influenza virus. J Virol 72(8):6637–6645PubMedCentralPubMedGoogle Scholar
  9. Brown DM, Dilzer AM, Meents DL, Swain SL (2006) CD4 T cell-mediated protection from lethal influenza: perforin and antibody-mediated mechanisms give a one-two punch. J Immunol 177(5):2888–2898PubMedCrossRefGoogle Scholar
  10. Brown DM, Lee S, Garcia-Hernandez Mde L, Swain SL (2012) Multifunctional CD4 cells expressing gamma interferon and perforin mediate protection against lethal influenza virus infection. J Virol 86(12):6792–6803. doi:10.1128/JVI.07172-11 PubMedCentralPubMedCrossRefGoogle Scholar
  11. Bushar ND, Corbo E, Schmidt M, Maltzman JS, Farber DL (2010) Ablation of SLP-76 signaling after T cell priming generates memory CD4 T cells impaired in steady-state and cytokine-driven homeostasis. Proc Natl Acad Sci U S A 107(2):827–831. doi:10.1073/pnas.0908126107 0908126107 [pii]
  12. Cepek KL, Shaw SK, Parker CM, Russell GJ, Morrow JS, Rimm DL, Brenner MB (1994) Adhesion between epithelial cells and T lymphocytes mediated by E- cadherin and the alpha E beta 7 integrin. Nature 372(6502):190–193PubMedCrossRefGoogle Scholar
  13. Cook DN, Beck MA, Coffman TM, Kirby SL, Sheridan JF, Pragnell IB, Smithies O (1995) Requirement of MIP-1 alpha for an inflammatory response to viral infection. Science 269(5230):1583–1585PubMedCrossRefGoogle Scholar
  14. Couceiro JN, Paulson JC, Baum LG (1993) Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity. Virus Res 29(2):155–165PubMedCrossRefGoogle Scholar
  15. Crotty S (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29:621–663. doi:10.1146/annurev-immunol-031210-101400 PubMedCrossRefGoogle Scholar
  16. Crowe CR, Chen K, Pociask DA, Alcorn JF, Krivich C, Enelow RI, Ross TM, Witztum JL, Kolls JK (2009) Critical role of IL-17RA in immunopathology of influenza infection. J Immunol 183(8):5301–5310. doi:10.4049/jimmunol.0900995 PubMedCentralPubMedCrossRefGoogle Scholar
  17. de Bree GJ, van Leeuwen EM, Out TA, Jansen HM, Jonkers RE, van Lier RA (2005) Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung. J Exp Med 202(10):1433–1442PubMedCentralPubMedCrossRefGoogle Scholar
  18. De Riva A, Bourgeois C, Kassiotis G, Stockinger B (2007) Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function. J Immunol 178(9):5488–5495PubMedCrossRefGoogle Scholar
  19. Dong J, Ivascu C, Chang HD, Wu P, Angeli R, Maggi L, Eckhardt F, Tykocinski L, Haefliger C, Mowes B, Sieper J, Radbruch A, Annunziato F, Thiel A (2007) IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes. J Immunol 179(4):2389–2396PubMedCrossRefGoogle Scholar
  20. Dudda JC, Simon JC, Martin S (2004) Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin: role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets. J Immunol 172(2):857–863PubMedCrossRefGoogle Scholar
  21. Epstein SL, Lo CY, Misplon JA, Lawson CM, Hendrickson BA, Max EE, Subbarao K (1997) Mechanisms of heterosubtypic immunity to lethal influenza A virus infection in fully immunocompetent, T cell-depleted, beta2-microglobulin-deficient, and J chain-deficient mice. J Immunol 158(3):1222–1230PubMedGoogle Scholar
  22. Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR (2009) Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol 10(5):524–530. doi:10.1038/ni.1718 ni.1718 [pii]
  23. Gerhard W (2001) The role of the antibody response in influenza virus infection. Curr Top Microbiol Immunol 260:171–190PubMedGoogle Scholar
  24. Gerhard W, Mozdzanowska K, Furchner M, Washko G, Maiese K (1997) Role of the B-cell response in recovery of mice from primary influenza virus infection. Immunol Rev 159:95–103PubMedCrossRefGoogle Scholar
  25. Graham MB, Braciale TJ (1997) Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice. J Exp Med 186(12):2063–2068PubMedCentralPubMedCrossRefGoogle Scholar
  26. Graham MB, Braciale VL, Braciale TJ (1994) Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection. J Exp Med 180(4):1273–1282PubMedCrossRefGoogle Scholar
  27. Graham MB, Dalton DK, Giltinan D, Braciale VL, Stewart TA, Braciale TJ (1993) Response to influenza infection in mice with a targeted disruption in the interferon gamma gene. J Exp Med 178(5):1725–1732PubMedCrossRefGoogle Scholar
  28. Hale JS, Youngblood B, Latner DR, Mohammed AU, Ye L, Akondy RS, Wu T, Iyer SS, Ahmed R (2013) Distinct memory CD4+ T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection. Immunity 38(4):805–817. doi:10.1016/j.immuni.2013.02.020 PubMedCentralPubMedCrossRefGoogle Scholar
  29. He XS, Holmes TH, Zhang C, Mahmood K, Kemble GW, Lewis DB, Dekker CL, Greenberg HB, Arvin AM (2006) Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol 80(23):11756–11766PubMedCentralPubMedCrossRefGoogle Scholar
  30. Hoft DF, Babusis E, Worku S, Spencer CT, Lottenbach K, Truscott SM, Abate G, Sakala IG, Edwards KM, Creech CB, Gerber MA, Bernstein DI, Newman F, Graham I, Anderson EL, Belshe RB (2011) Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J Infect Dis 204(6):845–853. doi:10.1093/infdis/jir436 PubMedCentralPubMedCrossRefGoogle Scholar
  31. Hogan RJ, Zhong W, Usherwood EJ, Cookenham T, Roberts AD, Woodland DL (2001) Protection from respiratory virus infections can be mediated by antigen-specific CD4(+) T cells that persist in the lungs. J Exp Med 193(8):981–986PubMedCentralPubMedCrossRefGoogle Scholar
  32. Hua L, Yao S, Pham D, Jiang L, Wright J, Sawant D, Dent AL, Braciale TJ, Kaplan MH, Sun J (2013) Cytokine-dependent induction of CD4+ T cells with cytotoxic potential during influenza virus infection. J Virol 87(21):11884–11893. doi:10.1128/JVI.01461-13 PubMedCentralPubMedCrossRefGoogle Scholar
  33. Huster KM, Busch V, Schiemann M, Linkemann K, Kerksiek KM, Wagner H, Busch DH (2004) Selective expression of IL-7 receptor on memory T cells identifies early CD40L-dependent generation of distinct CD8+ memory T cell subsets. Proc Natl Acad Sci U S A 101(15):5610–5615. doi:10.1073/pnas.0308054101 PubMedCentralPubMedCrossRefGoogle Scholar
  34. Jelley-Gibbs DM, Brown DM, Dibble JP, Haynes L, Eaton SM, Swain SL (2005) Unexpected prolonged presentation of influenza antigens promotes CD4 T cell memory generation. J Exp Med 202(5):697–706PubMedCentralPubMedCrossRefGoogle Scholar
  35. Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, Hagman J, Gapin L, Kaech SM (2007) Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27(2):281–295PubMedCentralPubMedCrossRefGoogle Scholar
  36. Julkunen I, Melen K, Nyqvist M, Pirhonen J, Sareneva T, Matikainen S (2000) Inflammatory responses in influenza A virus infection. Vaccine 19(Suppl 1):S32–S37PubMedCrossRefGoogle Scholar
  37. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R (2003) Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 4(12):1191–1198PubMedCrossRefGoogle Scholar
  38. Kaech SM, Wherry EJ (2007) Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity 27(3):393–405PubMedCentralPubMedCrossRefGoogle Scholar
  39. Kaech SM, Wherry EJ, Ahmed R (2002) Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol 2(4):251–262PubMedCrossRefGoogle Scholar
  40. Kassiotis G, Garcia S, Simpson E, Stockinger B (2002) Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nat Immunol 3(3):244–250PubMedCrossRefGoogle Scholar
  41. Kohlmeier JE, Cookenham T, Miller SC, Roberts AD, Christensen JP, Thomsen AR, Woodland DL (2009) CXCR3 directs antigen-specific effector CD4+ T cell migration to the lung during parainfluenza virus infection. J Immunol 183(7):4378–4384. doi:10.4049/jimmunol.0902022 jimmunol.0902022 [pii]
  42. Kohlmeier JE, Miller SC, Smith J, Lu B, Gerard C, Cookenham T, Roberts AD, Woodland DL (2008) The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections. Immunity 29(1):101–113PubMedCentralPubMedCrossRefGoogle Scholar
  43. Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD, Bradley LM (2003) Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med 198(12):1797–1806PubMedCentralPubMedCrossRefGoogle Scholar
  44. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485–517. doi:10.1146/annurev.immunol.021908.132710 10.1146/annurev.immunol.021908.132710 [pii]
  45. Lai W, Yu M, Huang MN, Okoye F, Keegan AD, Farber DL (2011) Transcriptional control of rapid recall by memory CD4 T cells. J Immunol 187(1):133–140. doi:10.4049/jimmunol.1002742 jimmunol.1002742 [pii]
  46. Lee LY, Ha DL, Simmons C, de Jong MD, Chau NV, Schumacher R, Peng YC, McMichael AJ, Farrar JJ, Smith GL, Townsend AR, Askonas BA, Rowland-Jones S, Dong T (2008) Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest 118(10):3478–3490PubMedCentralPubMedGoogle Scholar
  47. Lee YT, Suarez-Ramirez JE, Wu T, Redman JM, Bouchard K, Hadley GA, Cauley LS (2011) Environmental and antigen receptor-derived signals support sustained surveillance of the lungs by pathogen-specific cytotoxic T lymphocytes. J Virol 85(9):4085–4094. doi:10.1128/JVI.02493-10 PubMedCentralPubMedCrossRefGoogle Scholar
  48. Lenz DC, Kurz SK, Lemmens E, Schoenberger SP, Sprent J, Oldstone MB, Homann D (2004) IL-7 regulates basal homeostatic proliferation of antiviral CD4+ T cell memory. Proc Natl Acad Sci U S A 101(25):9357–9362PubMedCentralPubMedCrossRefGoogle Scholar
  49. Li J, Huston G, Swain SL (2003) IL-7 promotes the transition of CD4 effectors to persistent memory cells. J Exp Med 198(12):1807–1815PubMedCentralPubMedCrossRefGoogle Scholar
  50. Liang S, Mozdzanowska K, Palladino G, Gerhard W (1994) Heterosubtypic immunity to influenza type A virus in mice. Effector mechanisms and their longevity. J Immunol 152(4):1653–1661PubMedGoogle Scholar
  51. Liu L, Zhong Q, Tian T, Dubin K, Athale SK, Kupper TS (2010) Epidermal injury and infection during poxvirus immunization is crucial for the generation of highly protective T cell-mediated immunity. Nat Med 16(2):224–227. doi:10.1038/nm.2078 nm.2078 [pii]
  52. MacLeod MK, David A, McKee AS, Crawford F, Kappler JW, Marrack P (2011) Memory CD4 T cells that express CXCR5 provide accelerated help to B cells. J Immunol 186(5):2889–2896. doi:10.4049/jimmunol.1002955 PubMedCentralPubMedCrossRefGoogle Scholar
  53. Makgoba MW, Sanders ME, Ginther Luce GE, Dustin ML, Springer TA, Clark EA, Mannoni P, Shaw S (1988) ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature 331(6151):86–88. doi:10.1038/331086a0 PubMedCrossRefGoogle Scholar
  54. Masopust D, Choo D, Vezys V, Wherry EJ, Duraiswamy J, Akondy R, Wang J, Casey KA, Barber DL, Kawamura KS, Fraser KA, Webby RJ, Brinkmann V, Butcher EC, Newell KA, Ahmed R (2010) Dynamic T cell migration program provides resident memory within intestinal epithelium. J Exp Med 207(3):553–564. doi:10.1084/jem.20090858 jem.20090858 [pii]
  55. Masopust D, Vezys V, Marzo AL, Lefrancois L (2001) Preferential localization of effector memory cells in nonlymphoid tissue. Science 291(5512):2413–2417PubMedCrossRefGoogle Scholar
  56. Matsukura S, Kokubu F, Kubo H, Tomita T, Tokunaga H, Kadokura M, Yamamoto T, Kuroiwa Y, Ohno T, Suzaki H, Adachi M (1998) Expression of RANTES by normal airway epithelial cells after influenza virus A infection. Am J Respir Cell Mol Biol 18(2):255–264. doi:10.1165/ajrcmb.18.2.2822 PubMedCrossRefGoogle Scholar
  57. McKinstry KK, Golech S, Lee WH, Huston G, Weng NP, Swain SL (2007) Rapid default transition of CD4 T cell effectors to functional memory cells. J Exp Med 204(9):2199–2211PubMedCentralPubMedCrossRefGoogle Scholar
  58. McKinstry KK, Strutt TM, Buck A, Curtis JD, Dibble JP, Huston G, Tighe M, Hamada H, Sell S, Dutton RW, Swain SL (2009) IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge. J Immunol 182(12):7353–7363. doi:10.4049/jimmunol.0900657 PubMedCentralPubMedCrossRefGoogle Scholar
  59. McKinstry KK, Strutt TM, Kuang Y, Brown DM, Sell S, Dutton RW, Swain SL (2012) Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms. J Clin Invest 122(8):2847–2856. doi:10.1172/JCI63689 63689 [pii]
  60. Mikhak Z, Strassner JP, Luster AD (2013) Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4. J Exp Med 210(9):1855–1869. doi:10.1084/jem.20130091 PubMedCentralPubMedCrossRefGoogle Scholar
  61. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, Bridges CB (2007) The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 25(27):5086–5096. doi:10.1016/j.vaccine.2007.03.046 PubMedCrossRefGoogle Scholar
  62. Mora JR, Bono MR, Manjunath N, Weninger W, Cavanagh LL, Rosemblatt M, Von Andrian UH (2003) Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 424(6944):88–93PubMedCrossRefGoogle Scholar
  63. Mora JR, Cheng G, Picarella D, Briskin M, Buchanan N, von Andrian UH (2005) Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues. J Exp Med 201(2):303–316PubMedCentralPubMedCrossRefGoogle Scholar
  64. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, Foucat E, Dullaers M, Oh S, Sabzghabaei N, Lavecchio EM, Punaro M, Pascual V, Banchereau J, Ueno H (2011) Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 34(1):108–121. doi:10.1016/j.immuni.2010.12.012 S1074-S7613(10)00491-7 [pii]
  65. Moulton VR, Bushar ND, Leeser DB, Patke DS, Farber DL (2006) Divergent generation of heterogeneous memory CD4 T cells. J Immunol 177(2):869–876. doi:177/2/869 [pii]Google Scholar
  66. Mozdzanowska K, Maiese K, Gerhard W (2000) Th cell-deficient mice control influenza virus infection more effectively than Th- and B cell-deficient mice: evidence for a Th-independent contribution by B cells to virus clearance. J Immunol 164(5):2635–2643PubMedCrossRefGoogle Scholar
  67. Mueller SN, Gebhardt T, Carbone FR, Heath WR (2013) Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol 31:137–161. doi:10.1146/annurev-immunol-032712-095954 PubMedCrossRefGoogle Scholar
  68. Murdock BJ, Huffnagle GB, Olszewski MA, Osterholzer JJ (2013) IL-17A enhances host defense against cryptococcal lung infection through effects mediated by leukocyte recruitment, activation, and IFN-gamma production. Infect Immun. doi:10.1128/IAI.01477-13 PubMedGoogle Scholar
  69. O’Shea JJ, Paul WE (2010) Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327(5969):1098–1102. doi:10.1126/science.1178334 PubMedCentralPubMedCrossRefGoogle Scholar
  70. Osterholm MT, Kelley NS, Sommer A, Belongia EA (2012) Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12(1):36–44. doi:10.1016/S1473-3099(11)70295-X PubMedCrossRefGoogle Scholar
  71. Piet B, de Bree GJ, Smids-Dierdorp BS, van der Loos CM, Remmerswaal EB, von der Thusen JH, van Haarst JM, Eerenberg JP, Ten Brinke A, van der Bij W, Timens W, van Lier RA, Jonkers RE (2011) CD8+ T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung. J Clin Invest. doi:10.1172/JCI44675 44675 [pii]
  72. Purton JF, Tan JT, Rubinstein MP, Kim DM, Sprent J, Surh CD (2007) Antiviral CD4+ memory T cells are IL-15 dependent. J Exp Med 204(4):951–961. doi:10.1084/jem.20061805 PubMedCentralPubMedCrossRefGoogle Scholar
  73. Purwar R, Campbell J, Murphy G, Richards WG, Clark RA, Kupper TS (2011) Resident memory T cells (T(RM)) are abundant in human lung: diversity, function, and antigen specificity. PLoS One 6(1):e16245. doi:10.1371/journal.pone.0016245 PubMedCentralPubMedCrossRefGoogle Scholar
  74. Rathmell JC, Farkash EA, Gao W, Thompson CB (2001) IL-7 enhances the survival and maintains the size of naive T cells. J Immunol 167(12):6869–6876PubMedCrossRefGoogle Scholar
  75. Ray SJ, Franki SN, Pierce RH, Dimitrova S, Koteliansky V, Sprague AG, Doherty PC, de Fougerolles AR, Topham DJ (2004) The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity 20(2):167–179PubMedCrossRefGoogle Scholar
  76. Reinhardt RL, Khoruts A, Merica R, Zell T, Jenkins MK (2001) Visualizing the generation of memory CD4 T cells in the whole body. Nature 410(6824):101–105PubMedCrossRefGoogle Scholar
  77. Richards KA, Topham D, Chaves FA, Sant AJ (2010) Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus. J Immunol 185(9):4998–5002. doi:10.4049/jimmunol.1001395 PubMedCrossRefGoogle Scholar
  78. Ruane D, Brane L, Reis BS, Cheong C, Poles J, Do Y, Zhu H, Velinzon K, Choi JH, Studt N, Mayer L, Lavelle EC, Steinman RM, Mucida D, Mehandru S (2013) Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract. J Exp Med 210 (9):1871–1888. doi:10.1084/jem.2012276210.1084/jem.20122762
  79. Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763PubMedCrossRefGoogle Scholar
  80. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions [see comments]. Nature 401(6754):708–712PubMedCrossRefGoogle Scholar
  81. Sanders CJ, Doherty PC, Thomas PG (2010) Respiratory epithelial cells in innate immunity to influenza virus infection. Cell Tissue Res. doi:10.1007/s00441-010-1043-z PubMedGoogle Scholar
  82. Sandoval F, Terme M, Nizard M, Badoual C, Bureau MF, Freyburger L, Clement O, Marcheteau E, Gey A, Fraisse G, Bouguin C, Merillon N, Dransart E, Tran T, Quintin-Colonna F, Autret G, Thiebaud M, Suleman M, Riffault S, Wu TC, Launay O, Danel C, Taieb J, Richardson J, Zitvogel L, Fridman WH, Johannes L, Tartour E (2013) Mucosal imprinting of vaccine-induced CD8(+) T cells is crucial to inhibit the growth of mucosal tumors. Sci Transl Med 5(172):172ra120. doi:10.1126/scitranslmed.3004888
  83. Saraiva M, O’Garra A (2010) The regulation of IL-10 production by immune cells. Nat Rev Immunol 10(3):170–181. doi:10.1038/nri2711 PubMedCrossRefGoogle Scholar
  84. Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P, Thome JJ, Bickham KL, Lerner H, Goldstein M, Sykes M, Kato T, Farber DL (2013) Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 38(1):187–197. doi:10.1016/j.immuni.2012.09.020 S1074-7613(12)00521-3 [pii]
  85. Seddon B, Tomlinson P, Zamoyska R (2003) Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat Immunol 4(7):680–686PubMedCrossRefGoogle Scholar
  86. Shedlock DJ, Shen H (2003) Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science 300(5617):337–339PubMedCrossRefGoogle Scholar
  87. Shin H, Iwasaki A (2012) A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 491(7424):463–467. doi:10.1038/nature11522 nature11522 [pii]
  88. Shiow LR, Rosen DB, Brdickova N, Xu Y, An J, Lanier LL, Cyster JG, Matloubian M (2006) CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440(7083):540–544. doi:10.1038/nature04606 nature04606 [pii]
  89. Skon CN, Lee JY, Anderson KG, Masopust D, Hogquist KA, Jameson SC (2013) Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8(+) T cells. Nat Immunol 14(12):1285–1293. doi:10.1038/ni.2745 PubMedCrossRefGoogle Scholar
  90. Spensieri F, Borgogni E, Zedda L, Bardelli M, Buricchi F, Volpini G, Fragapane E, Tavarini S, Finco O, Rappuoli R, Del Giudice G, Galli G, Castellino F (2013) Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination, exert helper function, and predict antibody responses. Proc Natl Acad Sci U S A 110(35):14330–14335. doi:10.1073/pnas.1311998110 PubMedCentralPubMedCrossRefGoogle Scholar
  91. Sprenger H, Meyer RG, Kaufmann A, Bussfeld D, Rischkowsky E, Gemsa D (1996) Selective induction of monocyte and not neutrophil-attracting chemokines after influenza A virus infection. J Exp Med 184(3):1191–1196PubMedCrossRefGoogle Scholar
  92. Strutt TM, McKinstry KK, Dibble JP, Winchell C, Kuang Y, Curtis JD, Huston G, Dutton RW, Swain SL (2010) Memory CD4+ T cells induce innate responses independently of pathogen. Nat Med 16(5):558–564 (551 p following 564). doi:10.1038/nm.2142 nm.2142 [pii]
  93. Sun J, Madan R, Karp CL, Braciale TJ (2009) Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15(3):277–284PubMedCentralPubMedCrossRefGoogle Scholar
  94. Sun JC, Bevan MJ (2003) Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 300(5617):339–342PubMedCentralPubMedCrossRefGoogle Scholar
  95. Sun K, Torres L, Metzger DW (2010) A detrimental effect of interleukin-10 on protective pulmonary humoral immunity during primary influenza A virus infection. J Virol 84(10):5007–5014. doi:10.1128/JVI.02408-09 PubMedCentralPubMedCrossRefGoogle Scholar
  96. Tan JT, Dudl E, LeRoy E, Murray R, Sprent J, Weinberg KI, Surh CD (2001) IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A 98(15):8732–8737PubMedCentralPubMedCrossRefGoogle Scholar
  97. Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrancois L, Farber DL (2011) Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol 187(11):5510–5514. doi:10.4049/jimmunol.1102243 jimmunol.1102243 [pii]
  98. Teijaro JR, Verhoeven D, Page CA, Turner D, Farber DL (2010) Memory CD4 T cells direct protective responses to influenza virus in the lungs through helper-independent mechanisms. J Virol 84(18):9217-9226. doi:10.1128/JVI.01069-10 JVI.01069-10 [pii]
  99. Thatte J, Dabak V, Williams MB, Braciale TJ, Ley K (2003) LFA-1 is required for retention of effector CD8 T cells in mouse lungs. Blood 101(12):4916–4922PubMedCrossRefGoogle Scholar
  100. Thompson WW, Comanor L, Shay DK (2006) Epidemiology of seasonal influenza: use of surveillance data and statistical models to estimate the burden of disease. J Infect Dis 194(Suppl 2):S82–S91. doi:10.1086/507558 PubMedCrossRefGoogle Scholar
  101. Topham DJ, Tripp RA, Doherty PC (1997) CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J Immunol 159(11):5197–5200PubMedGoogle Scholar
  102. Turner DL, Bickham KL, Thome JJ, Kim CY, D’Ovidio F, Wherry EJ, Farber DL (2013) Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol. doi:10.1038/mi.2013.67 mi201367 [pii]
  103. Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, Kawakami K, Suda T, Sudo K, Nakae S, Iwakura Y, Matsuzaki G (2007) IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol 178(6):3786–3796PubMedCrossRefGoogle Scholar
  104. Wakim LM, Woodward-Davis A, Liu R, Hu Y, Villadangos J, Smyth G, Bevan MJ (2012) The molecular signature of tissue resident memory CD8 T cells isolated from the brain. J Immunol 189(7):3462–3471. doi:10.4049/jimmunol.1201305 jimmunol.1201305 [pii]
  105. Wareing MD, Lyon AB, Lu B, Gerard C, Sarawar SR (2004) Chemokine expression during the development and resolution of a pulmonary leukocyte response to influenza A virus infection in mice. J Leukoc Biol 76(4):886–895. doi:10.1189/jlb.1203644 PubMedCrossRefGoogle Scholar
  106. Weiss ID, Wald O, Wald H, Beider K, Abraham M, Galun E, Nagler A, Peled A (2010) IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner. J Interferon Cytokine Res 30(6):439–449. doi:10.1089/jir.2009.0084 PubMedCrossRefGoogle Scholar
  107. Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B, Staples KJ, Dong T, Douek DC, McMichael AJ, Xu XN (2012) Preexisting influenza-specific CD4(+) T cells correlate with disease protection against influenza challenge in humans. Nat Med 18(2):274–280. doi:10.1038/nm.2612 nm.2612 [pii]
  108. Woodland DL, Hogan RJ, Zhong W (2001) Cellular immunity and memory to respiratory virus infections. Immunol Res 24(1):53–67PubMedCrossRefGoogle Scholar
  109. Wu T, Hu Y, Lee YT, Bouchard KR, Benechet A, Khanna K, Cauley LS (2013) Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J Leukoc Biol. doi:10.1189/jlb.0313180
  110. Ye P, Garvey PB, Zhang P, Nelson S, Bagby G, Summer WR, Schwarzenberger P, Shellito JE, Kolls JK (2001a) Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am J Respir Cell Mol Biol 25(3):335–340. doi:10.1165/ajrcmb.25.3.4424 PubMedCrossRefGoogle Scholar
  111. Ye P, Rodriguez FH, Kanaly S, Stocking KL, Schurr J, Schwarzenberger P, Oliver P, Huang W, Zhang P, Zhang J, Shellito JE, Bagby GJ, Nelson S, Charrier K, Peschon JJ, Kolls JK (2001b) Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194(4):519–527PubMedCentralPubMedCrossRefGoogle Scholar
  112. Yu CI, Becker C, Wang Y, Marches F, Helft J, Leboeuf M, Anguiano E, Pourpe S, Goller K, Pascual V, Banchereau J, Merad M, Palucka K (2013) Human CD1c+ dendritic cells drive the differentiation of CD103+ CD8+ mucosal effector T cells via the cytokine TGF-beta. Immunity 38(4):818–830. doi:10.1016/j.immuni.2013.03.004 PubMedCentralPubMedCrossRefGoogle Scholar
  113. Zammit DJ, Turner DL, Klonowski KD, Lefrancois L, Cauley LS (2006) Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity 24(4):439–449PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Columbia Center for Translational ImmunologyColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Microbiology and ImmunologyColumbia University Medical CenterNew YorkUSA
  3. 3.Department of SurgeryColumbia University Medical CenterNew YorkUSA

Personalised recommendations