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CD8 T cells and Mycobacterium tuberculosis infection

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Abstract

Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. There is substantial evidence for the importance of CD4 T cells in control of tuberculosis, but the evidence for a requirement for CD8 T cells in this infection has not been proven in humans. However, animal model data support a non-redundant role for CD8 T cells in control of M. tuberculosis infection. In humans, infection with this pathogen leads to generation of specific CD8 T cell responses. These responses include classical (MHC Class I restricted) and non-classical CD8 T cells. Here, we discuss the potential roles of CD8 T cells in defense against tuberculosis, and our current understanding of the wide range of CD8 T cell types seen in M. tuberculosis infection.

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References

  1. Organization WH (2014) Global Tuberculosis Report 2014, World Health Organization

  2. Gideon HP, Phuah J, Myers AJ, Bryson BD, Rodgers MA, Coleman MT, Maiello P, Rutledge T, Marino S, Fortune SM, Kirschner DE, Lin PL, Flynn JL (2015) Variability in tuberculosis granuloma T cell responses exists, but a balance of Pro- and Anti-inflammatory cytokines is associated with sterilization. PLoS Pathog 11:e1004603

    Article  PubMed Central  PubMed  Google Scholar 

  3. Harriff MJ, Purdy GE, Lewinsohn DM (2012) Escape from the phagosome: the explanation for MHC-I processing of mycobacterial antigens? Front Immunol 3:40

    Article  PubMed Central  PubMed  Google Scholar 

  4. Harriff MJ, Cansler ME, Toren KG, Canfield ET, Kwak S, Gold MC, Lewinsohn DM (2014) Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8(+) T cells. PLoS One 9:e97515

    Article  PubMed Central  PubMed  Google Scholar 

  5. Mattila JT, Ojo OO, Kepka-Lenhart D, Marino S, Kim JH, Eum SY, Via LE, Barry CE 3rd, Klein E, Kirschner DE, Morris SM Jr, Lin PL, Flynn JL (2013) Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms. J Immunol 191:773–784

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Diedrich CR, Mattila JT, Klein E, Janssen C, Phuah J, Sturgeon TJ, Montelaro RC, Lin PL, Flynn JL (2010) Reactivation of latent tuberculosis in cynomolgus macaques infected with SIV is associated with early peripheral T cell depletion and not virus load. PLoS One 5:e9611

    Article  PubMed Central  PubMed  Google Scholar 

  7. Lin PL, Rutledge T, Green AM, Bigbee M, Fuhrman C, Klein E, Flynn JL (2012) CD4 T cell depletion exacerbates acute Mycobacterium tuberculosis while reactivation of latent infection is dependent on severity of tissue depletion in cynomolgus macaques. AIDS Res Hum Retrovir 28:1693–1702

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Orme IM (1987) The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J Immunol 138:293–298

    CAS  PubMed  Google Scholar 

  9. Serbina NV, Lazarevic V, Flynn JL (2001) CD4(+) T cells are required for the development of cytotoxic CD8(+) T cells during Mycobacterium tuberculosis infection. J Immunol 167:6991–7000

    Article  CAS  PubMed  Google Scholar 

  10. Serbina NV, Liu CC, Scanga CA, Flynn JL (2000) CD8+ CTL from lungs of Mycobacterium tuberculosis-infected mice express perforin in vivo and lyse infected macrophages. J Immunol 165:353–363

    Article  CAS  PubMed  Google Scholar 

  11. Mehra S, Golden NA, Dutta NK, Midkiff CC, Alvarez X, Doyle LA, Asher M, Russell-Lodrigue K, Monjure C, Roy CJ, Blanchard JL, Didier PJ, Veazey RS, Lackner AA, Kaushal D (2011) Reactivation of latent tuberculosis in rhesus macaques by coinfection with simian immunodeficiency virus. J Med Primatol 40:233–243

    Article  PubMed Central  PubMed  Google Scholar 

  12. Grotzke JE, Lewinsohn DM (2005) Role of CD8+ T lymphocytes in control of Mycobacterium tuberculosis infection. Microbes Infect 7:776–788

    Article  CAS  PubMed  Google Scholar 

  13. Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melian A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL (1998) An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282:121–125

    Article  CAS  PubMed  Google Scholar 

  14. Behar SM, Dascher CC, Grusby MJ, Wang CR, Brenner MB (1999) Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis. J Exp Med 189:1973–1980

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Flynn JL, Goldstein MM, Triebold KJ, Koller B, Bloom BR (1992) Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A 89:12013–12017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Sousa AO, Mazzaccaro RJ, Russell RG, Lee FK, Turner OC, Hong S, Van Kaer L, Bloom BR (2000) Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. Proc Natl Acad Sci U S A 97:4204–4208

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Schaible UE, Collins HL, Priem F, Kaufmann SH (2002) Correction of the iron overload defect in beta-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis. J Exp Med 196:1507–1513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. van Pinxteren LA, Cassidy JP, Smedegaard BH, Agger EM, Andersen P (2000) Control of latent Mycobacterium tuberculosis infection is dependent on CD8 T cells. Eur J Immunol 30:3689–3698

    Article  PubMed  Google Scholar 

  19. Chen CY, Huang D, Wang RC, Shen L, Zeng G, Yao S, Shen Y, Halliday L, Fortman J, McAllister M, Estep J, Hunt R, Vasconcelos D, Du G, Porcelli SA, Larsen MH, Jacobs WR Jr, Haynes BF, Letvin NL, Chen ZW (2009) A critical role for CD8 T cells in a nonhuman primate model of tuberculosis. PLoS Pathog 5:e1000392

    Article  PubMed Central  PubMed  Google Scholar 

  20. Lin PL, Pawar S, Myers A, Pegu A, Fuhrman C, Reinhart TA, Capuano SV, Klein E, Flynn JL (2006) Early events in Mycobacterium tuberculosis infection in cynomolgus macaques. Infect Immun 74:3790–3803

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Lin PL, Rodgers M, Smith L, Bigbee M, Myers A, Bigbee C, Chiosea I, Capuano SV, Fuhrman C, Klein E, Flynn JL (2009) Quantitative comparison of active and latent tuberculosis in the cynomolgus macaque model. Infect Immun 77:4631–4642

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Cho S, Mehra V, Thoma-Uszynski S, Stenger S, Serbina N, Mazzaccaro RJ, Flynn JL, Barnes PF, Southwood S, Celis E, Bloom BR, Modlin RL, Sette A (2000) Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis. Proc Natl Acad Sci U S A 97:12210–12215

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Matloubian M, Suresh M, Glass A, Galvan M, Chow K, Whitmire JK, Walsh CM, Clark WR, Ahmed R (1999) A role for perforin in downregulating T-cell responses during chronic viral infection. J Virol 73:2527–2536

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Cooper AM, D’Souza C, Frank AA, Orme IM (1997) The course of Mycobacterium tuberculosis infection in the lungs of mice lacking expression of either perforin- or granzyme-mediated cytolytic mechanisms. Infect Immun 65:1317–1320

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Hiebert PR, Granville DJ (2012) Granzyme B in injury, inflammation, and repair. Trends Mol Med 18:732–741

    Article  CAS  PubMed  Google Scholar 

  26. Silva BD, Trentini MM, da Costa AC, Kipnis A, Junqueira-Kipnis AP (2014) Different phenotypes of CD8+ T cells associated with bacterial load in active tuberculosis. Immunol Lett 160:23–32

    Article  CAS  PubMed  Google Scholar 

  27. Andersson J, Samarina A, Fink J, Rahman S, Grundstrom S (2007) Impaired expression of perforin and granulysin in CD8+ T cells at the site of infection in human chronic pulmonary tuberculosis. Infect Immun 75:5210–5222

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Mattila JT, Maiello P, Sun T, Via LE, Flynn JL (2015) Granzyme B-expressing neutrophils correlate with bacterial load in granulomas from Mycobacterium tuberculosis-infected cynomolgus macaques. Microbiol Cell. doi:10.1111/cmi.12428

    Google Scholar 

  29. Stenger S, Rosat JP, Bloom BR, Krensky AM, Modlin RL (1999) Granulysin: a lethal weapon of cytolytic T cells. Immunol Today 20:390–394

    Article  CAS  PubMed  Google Scholar 

  30. Krensky AM, Clayberger C (2009) Biology and clinical relevance of granulysin. Tissue Antigens 73:193–198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Walch M, Dotiwala F, Mulik S, Thiery J, Kirchhausen T, Clayberger C, Krensky AM, Martinvalet D, Lieberman J (2014) Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes. Cell 157:1309–1323

    Article  CAS  PubMed  Google Scholar 

  32. Ochoa MT, Stenger S, Sieling PA, Thoma-Uszynski S, Sabet S, Cho S, Krensky AM, Rollinghoff M, Nunes Sarno E, Burdick AE, Rea TH, Modlin RL (2001) T-cell release of granulysin contributes to host defense in leprosy. Nat Med 7:174–179

    Article  CAS  PubMed  Google Scholar 

  33. Caccamo N, Pietra G, Sullivan LC, Brooks AG, Prezzemolo T, La Manna MP, Di Liberto D, Joosten SA, van Meijgaarden KE, Di Carlo P, Titone L, Moretta L, Mingari MC, Ottenhoff TH, Dieli F (2015) Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines. Eur J Immunol. doi:10.1002/eji.201445193

    PubMed  Google Scholar 

  34. Prezzemolo T, Guggino G, La Manna MP, Di Liberto D, Dieli F, Caccamo N (2014) Functional signatures of human CD4 and CD8 T cell responses to Mycobacterium tuberculosis. Front Immunol 5:180

    Article  PubMed Central  PubMed  Google Scholar 

  35. Green AM, Mattila JT, Bigbee CL, Bongers KS, Lin PL, Flynn JL (2010) CD4(+) regulatory T cells in a cynomolgus macaque model of Mycobacterium tuberculosis infection. J Infect Dis 202:533–541

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Einarsdottir T, Lockhart E, Flynn JL (2009) Cytotoxicity and secretion of gamma interferon are carried out by distinct CD8 T cells during Mycobacterium tuberculosis infection. Infect Immun 77:4621–4630

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Rozot V, Vigano S, Mazza-Stalder J, Idrizi E, Day CL, Perreau M, Lazor-Blanchet C, Petruccioli E, Hanekom W, Goletti D, Bart PA, Nicod L, Pantaleo G, Harari A (2013) Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Eur J Immunol 43:1568–1577

    Article  CAS  PubMed  Google Scholar 

  38. Behar SM (2013) Antigen-specific CD8(+) T cells and protective immunity to tuberculosis. Adv Exp Med Biol 783:141–163

    Article  CAS  PubMed  Google Scholar 

  39. Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J, Winata E, Swarbrick GM, Chua WJ, Yu YY, Lantz O, Cook MS, Null MD, Jacoby DB, Harriff MJ, Lewinsohn DA, Hansen TH, Lewinsohn DM (2010) Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol 8:e1000407

    Article  PubMed Central  PubMed  Google Scholar 

  40. Lewinsohn DA, Winata E, Swarbrick GM, Tanner KE, Cook MS, Null MD, Cansler ME, Sette A, Sidney J, Lewinsohn DM (2007) Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B. PLoS Pathog 3:1240–1249

    Article  CAS  PubMed  Google Scholar 

  41. Lewinsohn DM, Briden AL, Reed SG, Grabstein KH, Alderson MR (2000) Mycobacterium tuberculosis-reactive CD8+ T lymphocytes: the relative contribution of classical versus nonclassical HLA restriction. J Immunol 165:925–930

    Article  CAS  PubMed  Google Scholar 

  42. Lewinsohn DM, Zhu L, Madison VJ, Dillon DC, Fling SP, Reed SG, Grabstein KH, Alderson MR (2001) Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells: definition of antigenic specificity. J Immunol 166:439–446

    Article  CAS  PubMed  Google Scholar 

  43. Urdahl KB, Liggitt D, Bevan MJ (2003) CD8+ T cells accumulate in the lungs of Mycobacterium tuberculosis-infected Kb−/−Db−/− mice, but provide minimal protection. J Immunol 170:1987–1994

    Article  CAS  PubMed  Google Scholar 

  44. Doi T, Yamada H, Yajima T, Wajjwalku W, Hara T, Yoshikai Y (2007) H2-M3-restricted CD8+ T cells induced by peptide-pulsed dendritic cells confer protection against Mycobacterium tuberculosis. J Immunol 178:3806–3813

    Article  CAS  PubMed  Google Scholar 

  45. Mir SA, Sharma S (2013) Role of MHC class Ib molecule, H2-M3 in host immunity against tuberculosis. Vaccine 31:3818–3825

    Article  CAS  PubMed  Google Scholar 

  46. Heinzel AS, Grotzke JE, Lines RA, Lewinsohn DA, McNabb AL, Streblow DN, Braud VM, Grieser HJ, Belisle JT, Lewinsohn DM (2002) HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells. J Exp Med 196:1473–1481

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Joosten SA, van Meijgaarden KE, van Weeren PC, Kazi F, Geluk A, Savage ND, Drijfhout JW, Flower DR, Hanekom WA, Klein MR, Ottenhoff TH (2010) Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity. PLoS Pathog 6:e1000782

    Article  PubMed Central  PubMed  Google Scholar 

  48. Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D (1998) HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391:397–401

    Article  CAS  PubMed  Google Scholar 

  49. Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL, Baltimore D (1999) The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10:661–671

    Article  CAS  PubMed  Google Scholar 

  50. Nattermann J, Nischalke HD, Hofmeister V, Kupfer B, Ahlenstiel G, Feldmann G, Rockstroh J, Weiss EH, Sauerbruch T, Spengler U (2005) HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells. Antivir Ther 10:95–107

    CAS  PubMed  Google Scholar 

  51. Rosat JP, Grant EP, Beckman EM, Dascher CC, Sieling PA, Frederique D, Modlin RL, Porcelli SA, Furlong ST, Brenner MB (1999) CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ alpha beta T cell pool. J Immunol 162:366–371

    CAS  PubMed  Google Scholar 

  52. Van Rhijn I, Moody DB (2015) CD1 and mycobacterial lipids activate human T cells. Immunol Rev 264:138–153

    Article  PubMed  Google Scholar 

  53. Torrelles JB, Sieling PA, Zhang N, Keen MA, McNeil MR, Belisle JT, Modlin RL, Brennan PJ, Chatterjee D (2012) Isolation of a distinct Mycobacterium tuberculosis mannose-capped lipoarabinomannan isoform responsible for recognition by CD1b-restricted T cells. Glycobiology 22:1118–1127

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Montamat-Sicotte DJ, Millington KA, Willcox CR, Hingley-Wilson S, Hackforth S, Innes J, Kon OM, Lammas DA, Minnikin DE, Besra GS, Willcox BE, Lalvani A (2011) A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection. J Clin Invest 121:2493–2503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Seshadri C, Thuong NT, Yen NT, Bang ND, Chau TT, Thwaites GE, Dunstan SJ, Hawn TR (2014) A polymorphism in human CD1A is associated with susceptibility to tuberculosis. Genes Immun 15:195–198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Dascher CC, Hiromatsu K, Xiong X, Morehouse C, Watts G, Liu G, McMurray DN, LeClair KP, Porcelli SA, Brenner MB (2003) Immunization with a mycobacterial lipid vaccine improves pulmonary pathology in the guinea pig model of tuberculosis. Int Immunol 15:915–925

    Article  CAS  PubMed  Google Scholar 

  57. Chen ZW, Letvin NL (2003) Adaptive immune response of Vgamma2Vdelta2 T cells: a new paradigm. Trends Immunol 24:213–219

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Shen Y, Zhou D, Qiu L, Lai X, Simon M, Shen L, Kou Z, Wang Q, Jiang L, Estep J, Hunt R, Clagett M, Sehgal PK, Li Y, Zeng X, Morita CT, Brenner MB, Letvin NL, Chen ZW (2002) Adaptive immune response of Vgamma2Vdelta2+ T cells during mycobacterial infections. Science 295:2255–2258

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Chen ZW (2013) Multifunctional immune responses of HMBPP-specific Vgamma2Vdelta2 T cells in M. tuberculosis and other infections. Cell Mol Immunol 10:58–64

    Article  PubMed Central  PubMed  Google Scholar 

  60. Gong G, Shao L, Wang Y, Chen CY, Huang D, Yao S, Zhan X, Sicard H, Wang R, Chen ZW (2009) Phosphoantigen-activated V gamma 2 V delta 2 T cells antagonize IL-2-induced CD4 + CD25 + Foxp3+ T regulatory cells in mycobacterial infection. Blood 113:837–845

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. He Y, Wu K, Hu Y, Sheng L, Tie R, Wang B, Huang H (2014) gammadelta T cell and other immune cells crosstalk in cellular immunity. J Immunol Res 2014:960252

    PubMed Central  PubMed  Google Scholar 

  62. Cummings JS, Cairo C, Armstrong C, Davis CE, Pauza CD (2008) Impacts of HIV infection on Vgamma2Vdelta2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS. J Leukoc Biol 84:371–379

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Le Bourhis L, Dusseaux M, Bohineust A, Bessoles S, Martin E, Premel V, Core M, Sleurs D, Serriari NE, Treiner E, Hivroz C, Sansonetti P, Gougeon ML, Soudais C, Lantz O (2013) MAIT cells detect and efficiently lyse bacterially-infected epithelial cells. PLoS Pathog 9:e1003681

    Article  PubMed Central  PubMed  Google Scholar 

  64. Dusseaux M, Martin E, Serriari N, Peguillet I, Premel V, Louis D, Milder M, Le Bourhis L, Soudais C, Treiner E, Lantz O (2011) Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117:1250–1259

    Article  CAS  PubMed  Google Scholar 

  65. Le Bourhis L, Martin E, Peguillet I, Guihot A, Froux N, Core M, Levy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O (2010) Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11:701–708

    Article  PubMed  Google Scholar 

  66. Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C, Premel V, Devys A, Moura IC, Tilloy F, Cherif S, Vera G, Latour S, Soudais C, Lantz O (2009) Stepwise development of MAIT cells in mouse and human. PLoS Biol 7:e54

    Article  PubMed  Google Scholar 

  67. Cyktor JC, Carruthers B, Beamer GL, Turner J (2013) Clonal expansions of CD8+ T cells with IL-10 secreting capacity occur during chronic Mycobacterium tuberculosis infection. PLoS One 8:e58612

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Boor PP, Metselaar HJ, Jonge S, Mancham S, van der Laan LJ, Kwekkeboom J (2011) Human plasmacytoid dendritic cells induce CD8(+) LAG-3(+) Foxp3(+) CTLA-4(+) regulatory T cells that suppress allo-reactive memory T cells. Eur J Immunol 41:1663–1674

    Article  CAS  PubMed  Google Scholar 

  69. Joosten SA, van Meijgaarden KE, Savage ND, de Boer T, Triebel F, van der Wal A, de Heer E, Klein MR, Geluk A, Ottenhoff TH (2007) Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci U S A 104:8029–8034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Boer MC, van Meijgaarden KE, Bastid J, Ottenhoff TH, Joosten SA (2013) CD39 is involved in mediating suppression by Mycobacterium bovis BCG-activated human CD8(+) CD39(+) regulatory T cells. Eur J Immunol 43:1925–1932

    Article  CAS  PubMed  Google Scholar 

  71. Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, Shea JE, McClain JB, Hussey GD, Hanekom WA, Mahomed H, McShane H, Team MATS (2013) Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381:1021–1028

    Article  CAS  PubMed  Google Scholar 

  72. Ottenhoff TH, Kaufmann SH (2012) Vaccines against tuberculosis: where are we and where do we need to go? PLoS Pathog 8:e1002607

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Behar SM, Woodworth JS, Wu Y (2007) Next generation: Tuberculosis vaccines that elicit protective CD8+ T cells. Expert Rev Vaccines 6:441–456

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Boom WH (2007) New TB vaccines: is there a requirement for CD8 T cells? J Clin Invest 117:2092–2094

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Betts G, Poyntz H, Stylianou E, Reyes-Sandoval A, Cottingham M, Hill A, McShane H (2012) Optimising immunogenicity with viral vectors: mixing MVA and HAdV-5 expressing the mycobacterial antigen Ag85A in a single injection. PLoS One 7:e50447

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Smaill F, Jeyanathan M, Smieja M, Medina MF, Thanthrige-Don N, Zganiacz A, Yin C, Heriazon A, Damjanovic D, Puri L, Hamid J, Xie F, Foley R, Bramson J, Gauldie J, Xing Z (2013) A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity. Sci Transl Med 5:205ra134

    Article  PubMed  Google Scholar 

  77. Perez de Val B, Vidal E, Villarreal-Ramos B, Gilbert SC, Andaluz A, Moll X, Martin M, Nofrarias M, McShane H, Vordermeier HM, Domingo M (2013) A multi-antigenic adenoviral-vectored vaccine improves BCG-induced protection of goats against pulmonary tuberculosis infection and prevents disease progression. PLoS One 8:e81317

    Article  PubMed Central  PubMed  Google Scholar 

  78. Dean G, Clifford D, Gilbert S, McShane H, Hewinson RG, Vordermeier HM, Villarreal-Ramos B (2014) Effect of dose and route of immunisation on the immune response induced in cattle by heterologous Bacille Calmette-Guerin priming and recombinant adenoviral vector boosting. Vet Immunol Immunopathol 158:208–213

    Article  CAS  PubMed  Google Scholar 

  79. Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser Eddine A, Mann P, Goosmann C, Bandermann S, Smith D, Bancroft GJ, Reyrat JM, van Soolingen D, Raupach B, Kaufmann SH (2005) Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin. J Clin Invest 115:2472–2479

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Sun R, Skeiky YA, Izzo A, Dheenadhayalan V, Imam Z, Penn E, Stagliano K, Haddock S, Mueller S, Fulkerson J, Scanga C, Grover A, Derrick SC, Morris S, Hone DM, Horwitz MA, Kaufmann SH, Sadoff JC (2009) Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis. Vaccine 27:4412–4423

    Article  CAS  PubMed  Google Scholar 

  81. Korsholm KS, Hansen J, Karlsen K, Filskov J, Mikkelsen M, Lindenstrom T, Schmidt ST, Andersen P, Christensen D (2014) Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant. Vaccine 32:3927–3935

    Article  CAS  PubMed  Google Scholar 

  82. Munier CM, Kelleher AD, Kent SJ, De Rose R (2013) The role of T cell immunity in HIV-1 infection. Curr Opin Virol 3:438–446

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Edwin Klein, D.V.M. for contributing the picture of the granuloma seen in Fig. 1. We thank Chelsea Chedrick for assistance with figures. We are grateful to all members of the Flynn and Lin laboratories for their insights and discussion. We acknowledge grant support from NIH (JLF: R01 AI50732, R01 AI37859, R01 HL106804, HL110811, R01 AI105422), the Bill and Melinda Gates Foundation (PLL and JLF), the Aeras Global TB Foundation (PLL and JLF), and the Otis Fund (Children’s Hospital of Pittsburgh of UPMC Foundation, PLL).

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Correspondence to JoAnne L. Flynn.

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This article is a contribution to the Special Issue on : CD8+ T-cell Responses against Non-Viral Pathogens - Guest Editors: Fidel Zavala and Imtiaz A. Khan

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Lin, P.L., Flynn, J.L. CD8 T cells and Mycobacterium tuberculosis infection. Semin Immunopathol 37, 239–249 (2015). https://doi.org/10.1007/s00281-015-0490-8

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