Ehrlich P. Collected studies on immunity. New York: J. Wiley; 1910.
Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat rev. 2005;5:772–82.CrossRef
Abbas AK, Lohr J, Knoechel B, Nagabhushanam V. T cell tolerance and autoimmunity. Autoimmun Rev. 2004;3:471–5.PubMedCrossRef
Curotto de Lafaille MA, Lafaille JJ. Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity. 2009;30:626–35.PubMedCrossRef
Kawahata K, et al. Generation of CD4(+)CD25(+) regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J Immunol. 2002;168:4399–405.PubMed
Apostolou I, Sarukhan A, Klein L, von Boehmer H. Origin of regulatory T cells with known specificity for antigen. Nat Immunol. 2002;3:756–63.PubMed
Jordan MS, et al. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol. 2001;2:301–6.PubMedCrossRef
Ghiringhelli F, et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Biol Med. 2005;202:1075–85.
Tang Q, et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol. 2003;171:3348–52.PubMed
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science (New York, NY). 2003; 299:1057–61.
Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330–6.PubMedCrossRef
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155:1151–64.PubMed
Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Biol Med. 2000;192:295–302.
Takahashi T, et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Biol Med. 2000;192:303–10.
McHugh RS, et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity. 2002;16:311–23.PubMedCrossRef
Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol. 2002;3:135–42.PubMedCrossRef
Walker MR, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest. 2003;112:1437–43.PubMed
Wang HY, et al. Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity. 2004;20:107–18.PubMedCrossRef
Baecher-Allan C, Viglietta V, Hafler DA. Human CD4+CD25+ regulatory T cells. Semin Immunol. 2004;16:89–98.PubMedCrossRef
Nishizuka Y, Sakakura T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science (New York, NY). 1969; 166:753–5.
Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol. 2003;4:337–42.PubMedCrossRef
Godfrey VL, Wilkinson JE, Russell LB. X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. Am J Pathol. 1991;138:1379–87.PubMed
Brunkow ME, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet. 2001;27:68–73.PubMedCrossRef
Bennett CL, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27:20–1.PubMedCrossRef
Chatila TA, et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest. 2000;106:R75–81.PubMedCrossRef
Wildin RS, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001;27:18–20.PubMedCrossRef
Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Biol Med. 2004;199:971–9.
Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes. 2005;54:92–9.PubMedCrossRef
Ehrenstein MR, et al. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Biol Med. 2004;200:277–85.
Curotto de Lafaille MA, Lafaille JJ. CD4(+) regulatory T cells in autoimmunity and allergy. Curr Opin Immunol. 2002;14:771–8.PubMedCrossRef
Wang HY, Wang RF. Regulatory T cells and cancer. Curr Opin Immunol. 2007;19:217–23.PubMedCrossRef
von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005;6:338–44.CrossRef
Piccirillo CA, Shevach EM. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol. 2001;167:1137–40.PubMed
Misra N, Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV. Cutting edge: human CD4+CD25+ T cells restrain the maturation and antigen-presenting function of dendritic cells. J Immunol. 2004;172:4676–80.PubMed
Lim HW, Hillsamer P, Banham AH, Kim CH. Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol. 2005;175:4180–3.PubMed
La Cava A, Van Kaer L, Fu Dong S. CD4+CD25+ Tregs and NKT cells: regulators regulating regulators. Trends Immunol. 2006;27:322–7.PubMedCrossRef
Taams LS, et al. Modulation of monocyte/macrophage function by human CD4+CD25+ regulatory T cells. Hum Immunol. 2005;66:222–30.PubMedCrossRef
Gri G, et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity. 2008;29:771–81.PubMedCrossRef
Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 2007;13:108–16.PubMedCrossRef
Rudensky AY, Campbell DJ. In vivo sites and cellular mechanisms of T reg cell-mediated suppression. J Exp Biol Med. 2006;203:489–92.
Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity. 2004;21:589–601.PubMedCrossRef
Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol. 2005;174:1783–6.PubMed
Cao X, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27:635–46.PubMedCrossRef
Bopp T, et al. Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J Exp Biol Med. 2007;204:1303–10.
Deaglio S, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Biol Med. 2007;204:1257–65.
Tadokoro CE, et al. Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J Exp Biol Med. 2006;203:505–11.
Tang Q, et al. Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol. 2006;7:83–92.PubMedCrossRef
Mills KH. Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol. 2004;4:841–55.PubMedCrossRef
Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol. 2005;6:353–60.PubMedCrossRef
Belkaid Y, et al. The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure. J Exp Biol Med. 2001;194:1497–506.
Suffia IJ, Reckling SK, Piccirillo CA, Goldszmid RS, Belkaid Y. Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. J Exp Biol Med. 2006;203:777–88.
Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature. 2002;420:502–7.PubMedCrossRef
Campanelli AP, et al. CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J Infect Dis. 2006;193:1313–22.PubMedCrossRef
Xu D, et al. Circulating and liver resident CD4+CD25+ regulatory T cells actively influence the antiviral immune response and disease progression in patients with hepatitis B. J Immunol. 2006;177:739–47.PubMed
Cavassani KA, et al. Systemic and local characterization of regulatory T cells in a chronic fungal infection in humans. J Immunol. 2006;177:5811–8.PubMed
Kandulski A, et al. Naturally occurring regulatory T cells (CD4+, CD25high, FOXP3+) in the antrum and cardia are associated with higher H. pylori colonization and increased gene expression of TGF-beta1. Helicobacter. 2008;13:295–303.PubMedCrossRef
Walther M, et al. Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity. 2005;23:287–96.PubMedCrossRef
Hisaeda H, et al. Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells. Nat Med. 2004;10:29–30.PubMedCrossRef
Ordway D, et al. The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation. J Immunol. 2007;179:522–31.PubMed
Suvas S, Azkur AK, Kim BS, Kumaraguru U, Rouse BT. CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions. J Immunol. 2004;172:4123–32.PubMed
Suvas S, Kumaraguru U, Pack CD, Lee S, Rouse BT. CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J Exp Biol Med. 2003;198:889–901.
Belkaid Y, Tarbell K. Regulatory T cells in the control of host-microorganism interactions (*). Annu Rev Immunol. 2009;27:551–89.PubMedCrossRef
Scott-Browne JP, et al. Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J Exp Biol Med. 2007;204:2159–69.
Quinn KM, et al. Inactivation of CD4+ CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load. Immunol Cell Biol. 2006;84:467–74.PubMedCrossRef
Montagnoli C, et al. B7/CD28-dependent CD4+CD25+ regulatory T cells are essential components of the memory-protective immunity to Candida albicans. J Immunol. 2002;169:6298–308.PubMed
McKinley L, Logar AJ, McAllister F, Zheng M, Steele C, Kolls JK. Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of pneumocystis pneumonia. J Immunol. 2006;177:6215–26.PubMed
Hesse M, et al. The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. J Immunol. 2004;172:3157–66.PubMed
Guilliams M, et al. African trypanosomiasis: naturally occurring regulatory T cells favor trypanotolerance by limiting pathology associated with sustained type 1 inflammation. J Immunol. 2007;179:2748–57.PubMed
Amante FH, et al. A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am J Pathol. 2007;171:548–59.PubMedCrossRef
Steeg C, Adler G, Sparwasser T, Fleischer B, Jacobs T. Limited role of CD4+Foxp3+ regulatory T cells in the control of experimental cerebral malaria. J Immunol. 2009;183:7014–22.PubMedCrossRef
Carrigan SO, et al. Depletion of natural CD4+CD25+ T regulatory cells with anti-CD25 antibody does not change the course of Pseudomonas aeruginosa-induced acute lung infection in mice. Immunobiology. 2009;214:211–22.PubMedCrossRef
Kotner J, Tarleton R. Endogenous CD4(+) CD25(+) regulatory T cells have a limited role in the control of Trypanosoma cruzi infection in mice. Infect Immun. 2007;75:861–9.PubMedCrossRef
Sales PA Jr, et al. The regulatory CD4+CD25+ T cells have a limited role on pathogenesis of infection with Trypanosoma cruzi. Microbes Infect. 2008;10:680–8.PubMedCrossRef
Couper KN, Blount DG, de Souza JB, Suffia I, Belkaid Y, Riley EM. Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice. J Immunol. 2007;178:4136–46.PubMed
Couper KN, et al. Anti-CD25 antibody-mediated depletion of effector T cell populations enhances susceptibility of mice to acute but not chronic Toxoplasma gondii infection. J Immunol. 2009;182:3985–94.PubMedCrossRef
Lund JM, Hsing L, Pham TT, Rudensky AY. Coordination of early protective immunity to viral infection by regulatory T cells. Science (New York, NY). 2008; 320:1220–4.
Kim JM, Rasmussen JP, Rudensky AY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol. 2007;8:191–7.PubMedCrossRef
Fulton RB, Meyerholz DK, Varga SM. Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J Immunol. 2010;185:2382–92.PubMedCrossRef
Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L. Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity. 2007;27:493–504.PubMedCrossRef
Hsieh CS, Zheng Y, Liang Y, Fontenot JD, Rudensky AY. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol. 2006;7:401–10.PubMedCrossRef
McKee AS, Pearce EJ. CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. J Immunol. 2004;173:1224–31.PubMed
Kinter AL, et al. CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J Exp Biol Med. 2004;200:331–43.
Huang X, Zhu J, Yang Y. Protection against autoimmunity in nonlymphopenic hosts by CD4+ CD25+ regulatory T cells is antigen-specific and requires IL-10 and TGF-beta. J Immunol. 2005;175:4283–91.PubMed
van Maren WW, Jacobs JF, de Vries IJ, Nierkens S, Adema GJ. Toll-like receptor signalling on Tregs: to suppress or not to suppress? Immunology. 2008;124:445–52.PubMedCrossRef
Chen Q, Davidson TS, Huter EN, Shevach EM. Engagement of TLR2 does not reverse the suppressor function of mouse regulatory T cells, but promotes their survival. J Immunol. 2009;183:4458–66.PubMedCrossRef
Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science (New York, NY). 2003; 299:1033–6.
Sather BD, et al. Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease. J Exp Biol Med. 2007;204:1335–47.
Schneider MA, Meingassner JG, Lipp M, Moore HD, Rot A. CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells. J Exp Biol Med. 2007;204:735–45.
Wei S, Kryczek I, Zou W. Regulatory T-cell compartmentalization and trafficking. Blood. 2006;108:426–31.PubMedCrossRef
Lehmann J, et al. Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells. Proc Natl Acad Sci USA. 2002;99:13031–6.PubMedCrossRef
Huehn J, et al. Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J Exp Biol Med. 2004;199:303–13.
Suffia I, Reckling SK, Salay G, Belkaid Y. A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J Immunol. 2005;174:5444–55.PubMed
Yurchenko E, Tritt M, Hay V, Shevach EM, Belkaid Y, Piccirillo CA. CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence. J Exp Biol Med. 2006;203:2451–60.
Moreira AP, et al. CCR5-dependent regulatory T cell migration mediates fungal survival and severe immunosuppression. J Immunol. 2008;180:3049–56.PubMed
Kroetz DN, Deepe GS, Jr. CCR5 dictates the equilibrium of proinflammatory IL-17+ and regulatory Foxp3+ T cells in fungal infection. J Immunol. 2010;184:5224–31.PubMedCrossRef