Regulatory T cells: friend or foe in immunity to infection? (original) (raw)

• Artavanis-Tsakonas, K., Tongren, J. E. & Riley, E. M. The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. Clin. Exp. Immunol. 133, 145–152 (2003).
  CAS PubMed PubMed Central Google Scholar
• von Herrath, M. G. & Harrison, L. C. Antigen-induced regulatory T cells in autoimmunity. Nature Rev. Immunol. 3, 223–232 (2003).
  CAS Google Scholar
• Redpath, S., Ghazal, P. & Gascoigne, N. R. Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol. 9, 86–92 (2001).
  CAS PubMed Google Scholar
• Reed, S. G. TGF-β in infections and infectious diseases. Microbes Infect. 1, 1313–1325 (1999).
  CAS PubMed Google Scholar
• Yazdanbakhsh, M., Kremsner, P. G. & van Ree, R. Allergy, parasites, and the hygiene hypothesis. Science 296, 490–494 (2002).
  CAS PubMed Google Scholar
• Braun-Fahrlander, C. et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N. Engl. J. Med. 347, 869–877 (2002).
  PubMed Google Scholar
• Mills, K. H. G. & Boyd, A. in Topley and Wilsons's Microbiology and Microbial Infections 10th edn (eds Kaufmann, S. H. & Steward, M.) (Edward Arnold Publishers Ltd, London, in press).
• McGuirk, P. & Mills, K. H. G. Pathogen-specific regulatory T cells provoke a shift in the TH1/TH2 paradigm in immunity to infectious diseases. Trends Immunol. 23, 450–455 (2002).
  CAS PubMed Google Scholar
• Cozzo, C., Larkin, J. & Caton, A. J. Self-peptides drive the peripheral expansion of CD4+CD25+ regulatory T cells. J. Immunol. 171, 5678–5682 (2003).
  CAS PubMed Google Scholar
• Bluestone, J. A. & Abbas, A. K. Natural versus adaptive regulatory T cells. Nature Rev. Immunol. 3, 253–257 (2003).
  CAS Google Scholar
• Garba, M. L., Pilcher, C. D., Bingham, A. L., Eron, J. & Frelinger, J. A. HIV antigens can induce TGF-β1-producing immunoregulatory CD8+ T cells. J. Immunol. 168, 2247–2254 (2002).
  CAS PubMed Google Scholar
• Haynes, L. M., Vanderlugt, C. L., Dal Canto, M. C., Melvold, R. W. & Miller, S. D. CD8+ T cells from Theiler's virus-resistant BALB/cByJ mice downregulate pathogenic virus-specific CD4+ T cells. J. Neuroimmunol. 106, 43–52 (2000).
  CAS PubMed Google Scholar
• Harrison, L. C., Dempsey-Collier, M., Kramer, D. R. & Takahashi, K. Aerosol insulin induces regulatory CD8 γδ T cells that prevent murine insulin-dependent diabetes. J. Exp. Med. 184, 2167–2174 (1996).
  CAS PubMed PubMed Central Google Scholar
• Seo, N., Tokura, Y., Takigawa, M. & Egawa, K. Depletion of IL-10- and TGF-β-producing regulatory γδ T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells. J. Immunol. 163, 242–249 (1999).
  CAS PubMed Google Scholar
• Sonoda, K. H. et al. NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J. Immunol. 166, 42–50 (2001).
  CAS PubMed Google Scholar
• Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151–1164 (1995). The first description of CD25 as a marker for T Reg cells and the demonstration that these cells can suppress immune responses that mediate autoimmune diseases.
  CAS PubMed Google Scholar
• Powrie, F., Carlino, J., Leach, M. W., Mauze, S. & Coffman, R. L. A critical role for transforming growth factor-β but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RBlowCD4+ T cells. J. Exp. Med. 183, 2669–2674 (1996).
  Article CAS PubMed Google Scholar
• Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y. & Sakaguchi, S. Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nature Immunol. 3, 135–142 (2002).
  CAS Google Scholar
• Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol. 4, 330–336 (2003).
  CAS Google Scholar
• Hori, S., Nomura, T. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057–1061 (2003).
  CAS PubMed Google Scholar
• Richman, L. K., Chiller, J. M., Brown, W. R., Hanson, D. G. & Vaz, N. M. Enterically induced immunologic tolerance. I. Induction of suppressor T lymphocytes by intragastric administration of soluble proteins. J. Immunol. 121, 2429–2434 (1978).
  CAS PubMed Google Scholar
• Miller, A., Lider, O., Roberts, A. B., Sporn, M. B. & Weiner, H. L. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor-β after antigen-specific triggering. Proc. Natl Acad. Sci. USA 89, 421–425 (1992).
  CAS PubMed PubMed Central Google Scholar
• Hirai, K. et al. Suppression of cell-mediated immunity by street rabies virus infection. Microbiol. Immunol. 36, 1277–1290 (1992).
  CAS PubMed Google Scholar
• Mahanty, S. et al. High levels of spontaneous and parasite antigen-driven interleukin-10 production are associated with antigen-specific hyporesponsiveness in human lymphatic filariasis. J. Infect. Dis. 173, 769–773 (1996).
  CAS PubMed Google Scholar
• Boussiotis, V. A. et al. IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J. Clin. Invest. 105, 1317–1325 (2000).
  CAS PubMed PubMed Central Google Scholar
• Chen, Y., Kuchroo, V. K., Inobe, J., Hafler, D. A. & Weiner, H. L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237–1240 (1994).
  CAS PubMed Google Scholar
• Groux, H. et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737–742 (1997). The first description of T R 1-cell clones and their ability to prevent inflammatory disease.
  CAS PubMed Google Scholar
• McGuirk, P., McCann, C. & Mills, K. H. G. Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J. Exp. Med. 195, 221–231 (2002). The first demonstration of T R 1 cells specific for a bacterial antigen, their cloning from a mucosal site of infection and a role for IL-10 produced by DCs in their induction.
  CAS PubMed PubMed Central Google Scholar
• Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M. & Sacks, D. L. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420, 502–507 (2002). The first description of a role for CD4+CD25+ T Reg cells in protective immunity to infection and in the development of immunological memory to a parasite.
  CAS PubMed Google Scholar
• Lundgren, A., Suri-Payer, E., Enarsson, K., Svennerholm, A. M. & Lundin, B. S. _Helicobacter pylori_-specific CD4+CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infect. Immun. 71, 1755–1762 (2003).
  CAS PubMed PubMed Central Google Scholar
• Vahlenkamp, T. W., Tompkins, M. B. & Tompkins, W. A. Feline immunodeficiency virus infection phenotypically and functionally activates immunosuppressive CD4+CD25+ T regulatory cells. J. Immunol. 172, 4752–4761 (2004).
  CAS PubMed Google Scholar
• Lavelle, E. C. et al. Cholera toxin promotes the induction of regulatory T cells specific for bystander antigens by modulating dendritic cell activation. J. Immunol. 171, 2384–2392 (2003).
  CAS PubMed Google Scholar
• Cottrez, F., Hurst, S. D., Coffman, R. L. & Groux, H. T regulatory cells 1 inhibit a TH2-specific response in vivo. J. Immunol. 165, 4848–4853 (2000).
  CAS PubMed Google Scholar
• Piccirillo, C. A. & Shevach, E. M. Control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J. Immunol. 167, 1137–1140 (2001).
  CAS PubMed Google Scholar
• Kursar, M. et al. Regulatory CD4+CD25+ T cells restrict memory CD8+ T cell responses. J. Exp. Med. 196, 1585–1592 (2002).
  CAS PubMed PubMed Central Google Scholar
• Suvas, S., Kumaraguru, U., Pack, C. D., Lee, S. & Rouse, B. T. CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J. Exp. Med. 198, 889–901 (2003).
  CAS PubMed PubMed Central Google Scholar
• Maloy, K. J. et al. CD4+CD25+ TR cells suppress innate immune pathology through cytokine-dependent mechanisms. J. Exp. Med. 197, 111–119 (2003). This paper describes the role of CD45RB hi T Reg cells in the prevention of bacteria-induced inflammation in the intestine.
  Article CAS PubMed PubMed Central Google Scholar
• Kitani, A., Chua, K., Nakamura, K. & Strober, W. Activated self-MHC-reactive T cells have the cytokine phenotype of TH3/T regulatory cell 1 T cells. J. Immunol. 165, 691–702 (2000).
  CAS PubMed Google Scholar
• Gorelik, L., Constant, S. & Flavell, R. A. Mechanism of transforming growth factor β-induced inhibition of T helper type 1 differentiation. J. Exp. Med. 195, 1499–1505 (2002).
  CAS PubMed PubMed Central Google Scholar
• Moore, K. W., de Waal Malefyt, R., Coffman, R. L. & O'Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683–765 (2001).
  CAS PubMed Google Scholar
• Kitani, A. et al. Transforming growth factor (TGF)-β1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-β1-mediated fibrosis. J. Exp. Med. 198, 1179–1188 (2003).
  CAS PubMed PubMed Central Google Scholar
• Grundstrom, S., Cederbom, L., Sundstedt, A., Scheipers, P. & Ivars, F. Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural CD4+CD25+ regulatory T cells in vivo. J. Immunol. 170, 5008–5017 (2003).
  PubMed Google Scholar
• 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. Med. 192, 295–302 (2000).
  CAS PubMed PubMed Central Google Scholar
• Nakamura, K., Kitani, A. & Strober, W. Cell contact-dependent immunosuppression by CD4+CD25+ regulatory T cells is mediated by cell surface-bound transforming growth factor-β. J. Exp. Med. 194, 629–644 (2001).
  CAS PubMed PubMed Central Google Scholar
• Barthlott, T., Kassiotis, G. & Stockinger, B. T cell regulation as a side effect of homeostasis and competition. J. Exp. Med. 197, 451–460 (2003).
  CAS PubMed PubMed Central Google Scholar
• MacDonald, A. J. et al. CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons. J. Infect. Dis. 185, 720–727 (2002).
  CAS PubMed Google Scholar
• Doetze, A. et al. Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by TH3/TR1-type cytokines IL-10 and transforming growth factor-β but not by a TH1 to TH2 shift. Int. Immunol. 12, 623–630 (2000). The first demonstration of parasite-specific T R 1 and T H 3 cells at the clonal level in humans.
  CAS PubMed Google Scholar
• Satoguina, J. et al. Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microbes Infect. 4, 1291–1300 (2002).
  CAS PubMed Google Scholar
• Accapezzato, D. et al. Hepatic expansion of a virus-specific regulatory CD8+ T cell population in chronic hepatitis C virus infection. J. Clin. Invest. 113, 963–972 (2004).
  CAS PubMed PubMed Central Google Scholar
• Marshall, N. A., Vickers, M. A. & Barker, R. N. Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1. J. Immunol. 170, 6183–6189 (2003).
  CAS PubMed Google Scholar
• Delgado, J. C. et al. Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia. Proc. Natl Acad. Sci. USA 99, 7576–7581 (2002).
  CAS PubMed PubMed Central Google Scholar
• Gerosa, F. et al. CD4+ T cell clones producing both interferon-γ and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients. Clin. Immunol. 92, 224–234 (1999).
  CAS PubMed Google Scholar
• Ostrowski, M. A. et al. Quantitative and qualitative assessment of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cell immunity to gag in HIV-1-infected individuals with differential disease progression: reciprocal interferon-γ and interleukin-10 responses. J. Infect. Dis. 184, 1268–1278 (2001).
  CAS PubMed Google Scholar
• Beilharz, M. W. et al. Timed ablation of regulatory CD4+ T cells can prevent murine AIDS progression. J. Immunol. 172, 4917–4925 (2004).
  CAS PubMed Google Scholar
• van der Kleij, D. et al. A novel host–parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J. Biol. Chem. 277, 48122–48129 (2002).
  CAS PubMed Google Scholar
• Kullberg, M. C. et al. Bacteria-triggered CD4+ T regulatory cells suppress _Helicobacter hepaticus_-induced colitis. J. Exp. Med. 196, 505–515 (2002).
  CAS PubMed PubMed Central Google Scholar
• Graca, L., Le Moine, A., Cobbold, S. P. & Waldmann, H. Dominant transplantation tolerance. Curr. Opin. Immunol. 15, 499–506 (2003).
  CAS PubMed Google Scholar
• Chen, C., Lee, W. H., Yun, P., Snow, P. & Liu, C. P. Induction of autoantigen-specific TH2 and TR1 regulatory T cells and modulation of autoimmune diabetes. J. Immunol. 171, 733–744 (2003).
  CAS PubMed Google Scholar
• Akdis, M. et al. Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J. Exp. Med. 199, 1567–1575 (2004).
  CAS PubMed PubMed Central Google Scholar
• Brady, M. T., MacDonald, A. J., Rowan, A. G. & Mills, K. H. Hepatitis C virus non-structural protein 4 suppresses TH1 responses by stimulating IL-10 production from monocytes. Eur. J. Immunol. 33, 3448–3457 (2003).
  CAS PubMed Google Scholar
• Boyer, O. et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 103, 3428–3430 (2004).
  CAS PubMed Google Scholar
• Suvas, S., Azkur, A. K., Kim, B. S., Kumaraguru, U. & Rouse, B. T. CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions. J. Immunol. 172, 4123–4132 (2004). This study shows that CD25+ T Reg cells suppress CD4+ T-cell responses in vivo and limit inflammation during corneal infection with HSV.
  CAS PubMed Google Scholar
• Deckert, M. et al. Endogenous interleukin-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis. Infect. Immun. 69, 4561–4571 (2001).
  CAS PubMed PubMed Central Google Scholar
• Sewnath, M. E. et al. IL-10-deficient mice demonstrate multiple organ failure and increased mortality during Escherichia coli peritonitis despite an accelerated bacterial clearance. J. Immunol. 166, 6323–6331 (2001).
  CAS PubMed Google Scholar
• Chen, W., Shu, D. & Chadwick, V. S. Helicobacter pylori infection: mechanism of colonization and functional dyspepsia. Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10. J. Gastroenterol. Hepatol. 16, 377–383 (2001).
  PubMed Google Scholar
• Kullberg, M. C. et al. _Helicobacter hepaticus_-induced colitis in interleukin-10-deficient mice: cytokine requirements for the induction and maintenance of intestinal inflammation. Infect. Immun. 69, 4232–4241 (2001).
  CAS PubMed PubMed Central Google Scholar
• Higgins, S. C. et al. Toll-like receptor 4-mediated innate IL-10 activates antigen-specific regulatory T cells and confers resistance to Bordetella pertussis by inhibiting inflammatory pathology. J. Immunol. 171, 3119–3127 (2003). This paper describes a role for TLR4 in the induction of IL-10 production by innate immune cells and regulatory T cells and its role in preventing bacteria-induced lung inflammation.
  CAS PubMed Google Scholar
• Raghavan, S., Fredriksson, M., Svennerholm, A. M., Holmgren, J. & Suri-Payer, E. Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in _Helicobacter pylori_-infected mice. Clin. Exp. Immunol. 132, 393–400 (2003).
  CAS PubMed PubMed Central Google Scholar
• Hori, S., Carvalho, T. L. & Demengeot, J. CD25+CD4+ regulatory T cells suppress CD4+ T cell-mediated pulmonary hyperinflammation driven by Pneumocystis carinii in immunodeficient mice. Eur. J. Immunol. 32, 1282–1291 (2002). This paper shows that regulatory T cells can increase the pathogen load but protect the host by limiting lung inflammation and the wasting syndrome induced by P. carinii.
  CAS PubMed Google Scholar
• 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. 169, 6298–6308 (2002).
  CAS PubMed Google Scholar
• Netea, M. G. et al. Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells. J. Immunol. 172, 3712–3718 (2004).
  CAS PubMed Google Scholar
• May, J., Lell, B., Luty, A. J., Meyer, C. G. & Kremsner, P. G. Plasma interleukin-10: tumor necrosis factor (TNF)-α ratio is associated with TNF promoter variants and predicts malarial complications. J. Infect. Dis. 182, 1570–1573 (2000).
  CAS PubMed Google Scholar
• Othoro, C. et al. A low interleukin-10 tumor necrosis factor-α ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. J. Infect. Dis. 179, 279–282 (1999).
  CAS PubMed Google Scholar
• Li, C., Corraliza, I. & Langhorne, J. A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice. Infect. Immun. 67, 4435–4442 (1999).
  CAS PubMed PubMed Central Google Scholar
• Omer, F. M. & Riley, E. M. Transforming growth factor-β production is inversely correlated with severity of murine malaria infection. J. Exp. Med. 188, 39–48 (1998).
  CAS PubMed PubMed Central Google Scholar
• Omer, F. M., de Souza, J. B. & Riley, E. M. Differential induction of TGF-β regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections. J. Immunol. 171, 5430–5436 (2003).
  CAS PubMed Google Scholar
• Hesse, M. et al. The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. J. Immunol. 172, 3157–3166 (2004).
  CAS PubMed Google Scholar
• Xu, D. et al. CD4+CD25+ regulatory T cells suppress differentiation and functions of TH1 and TH2 cells, Leishmania major infection and colitis in mice. J. Immunol. 170, 394–399 (2003).
  CAS PubMed Google Scholar
• Sugimoto, K. et al. Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 38, 1437–1448 (2003).
  PubMed Google Scholar
• Clerici, M. & Shearer, G. M. The TH1–TH2 hypothesis of HIV infection: new insights. Immunol. Today 15, 575–581 (1994).
  CAS PubMed Google Scholar
• Kinter, A. L. 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. Med. 200, 331–343 (2004).
  CAS PubMed PubMed Central Google Scholar
• Aandahl, E. M., Michaelsson, J., Moretto, W. J., Hecht, F. M. & Nixon, D. F. Human CD4+CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens. J. Virol. 78, 2454–2459 (2004).
  CAS PubMed PubMed Central Google Scholar
• Iwashiro, M. et al. Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection. Proc. Natl Acad. Sci. USA 98, 9226–9230 (2001).
  CAS PubMed PubMed Central Google Scholar
• Dittmer, U. et al. Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection. Immunity 20, 293–303 (2004). This study describes a role for IL-10-secreting CD4+ regulatory T cells in suppressing the protective effect of CD8+ CTLs in a viral infection.
  CAS PubMed Google Scholar
• Turner, J. et al. In vivo IL-10 production reactivates chronic pulmonary tuberculosis in C57BL/6 mice. J. Immunol. 169, 6343–6351 (2002).
  CAS PubMed Google Scholar
• Jacobs, M., Brown, N., Allie, N., Gulert, R. & Ryffel, B. Increased resistance to mycobacterial infection in the absence of interleukin-10. Immunology 100, 494–501 (2000).
  CAS PubMed PubMed Central Google Scholar
• Sing, A., Roggenkamp, A., Geiger, A. M. & Heesemann, J. Yersinia enterocolitica evasion of the host innate immune response by V antigen-induced IL-10 production of macrophages is abrogated in IL-10-deficient mice. J. Immunol. 168, 1315–1321 (2002).
  CAS PubMed Google Scholar
• Ross, P. J., Lavelle, E. C., Mills, K. H. G. & Boyd, A. P. Adenylate cyclase toxin from Bordetella pertussis synergises with lipopolysaccaride to promote innate IL-10 production and enhance the induction of TH2 and regulatory T cells. Infect. Immun. 72, 1568–1579 (2003).
  Google Scholar
• McGuirk, P., Mahon, B. P., Griffin, F. & Mills, K. H. G. Compartmentalization of T cell responses following respiratory infection with Bordetella pertussis: hyporesponsiveness of lung T cells is associated with modulated expression of the co-stimulatory molecule CD28. Eur. J. Immunol. 28, 153–163 (1998).
  CAS PubMed Google Scholar
• Kursar, M., Kohler, A., Kaufmann, S. H. & Mittrucker, H. W. Depletion of CD4+ T cells during immunization with nonviable Listeria monocytogenes causes enhanced CD8+ T cell-mediated protection against listeriosis. J. Immunol. 172, 3167–3172 (2004).
  CAS PubMed Google Scholar
• Hisaeda, H. et al. Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells. Nature Med. 10, 29–30 (2004). This study shows that depletion of natural regulatory T cells allows the host immune response to clear a parasite infection.
  CAS PubMed Google Scholar
• Long, T. T., Nakazawa, S., Onizuka, S., Huaman, M. C. & Kanbara, H. Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice. Int. J. Parasitol. 33, 175–183 (2003).
  CAS PubMed Google Scholar
• Noben-Trauth, N., Lira, R., Nagase, H., Paul, W. E. & Sacks, D. L. The relative contribution of IL-4 receptor signaling and IL-10 to susceptibility to Leishmania major. J. Immunol. 170, 5152–5158 (2003).
  CAS PubMed Google Scholar
• Sacks, D. & Noben-Trauth, N. The immunology of susceptibility and resistance to Leishmania major in mice. Nature Rev. Immunol. 2, 845–858 (2002).
  CAS Google Scholar
• Jonuleit, H., Schmitt, E., Schuler, G., Knop, J. & Enk, A. H. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192, 1213–1222 (2000).
  CAS PubMed PubMed Central Google Scholar
• Martin, E., O'Sullivan, B., Low, P. & Thomas, R. Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 18, 155–167 (2003).
  CAS PubMed Google Scholar
• von der Weid, T., Bulliard, C. & Schiffrin, E. J. Induction by a lactic acid bacterium of a population of CD4+ T cells with low proliferative capacity that produce transforming growth factor-β and interleukin-10. Clin. Diagn. Lab. Immunol. 8, 695–701 (2001).
  CAS PubMed PubMed Central Google Scholar
• Caramalho, I. et al. Regulatory T cells selectively express Toll-like receptors and are activated by lipopolysaccharide. J. Exp. Med. 197, 403–411 (2003).
  CAS PubMed PubMed Central Google Scholar
• Kemper, C. et al. Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421, 388–392 (2003).
  CAS PubMed Google Scholar
• Mendez, S., Reckling, S. K., Piccirillo, C. A., Sacks, D. & Belkaid, Y. Role for CD4+CD25+ regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J. Exp. Med. 200, 201–210 (2004).
  CAS PubMed PubMed Central Google Scholar
• Bynoe, M. S., Evans, J. T., Viret, C. & Janeway, C. A. Jr. Epicutaneous immunization with autoantigenic peptides induces T suppressor cells that prevent experimental allergic encephalomyelitis. Immunity 19, 317–328 (2003).
  CAS PubMed Google Scholar
• Golgher, D., Jones, E., Powrie, F., Elliott, T. & Gallimore, A. Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur. J. Immunol. 32, 3267–3275 (2002).
  CAS PubMed Google Scholar