• 1
    Montoya, J. G. and Liesenfeld, O., Toxoplasmosis. Lancet 2004. 363: 19651976.
  • 2
    Gazzinelli, R. T., Wysocka, M., Hayashi, S., Denkers, E.Y., Hieny, S., Caspar, P., Trinchieri, G. and Sher, A., Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J. Immunol. 1994. 153: 25332543.
  • 3
    Liu, C. H., Fan, Y.T., Dias, A., Esper, L., Corn, R. A., Bafica, A., Machado, F. S. and Aliberti, J., Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice. J. Immunol. 2006. 177: 3135.
  • 4
    Suzuki, Y., Orellana, M. A., Schreiber, R. D. and Remington, J. S., Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science 1988. 240: 516518.
  • 5
    Denkers, E. Y. and Gazzinelli, R. T., Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin. Microbiol. Rev. 1998. 11: 569588.
  • 6
    Gazzinelli, R. T., Amichay, D., Sharton-Kersten, T., Grunwald, E., Farber, J. M. and Sher, A., Role of macrophage-derived cytokines in the induction and regulation of cell-mediated immunity to Toxoplasma gondii. Curr. Top. Microbiol. Immunol. 1996. 219: 127139.
  • 7
    Lykens, J. E., Terrell, C. E., Zoller, E. E., Divanovic, S., Trompette, A., Karp, C. L., Aliberti, J. et al., Mice with a selective impairment of IFN-gamma signaling in macrophage lineage cells demonstrate the critical role of IFN-gamma-activated macrophages for the control of protozoan parasitic infections in vivo. J. Immunol. 2010. 184: 877885.
  • 8
    Suzuki, Y. and Remington, J. S., Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice. J. Immunol. 1988. 140: 39433946.
  • 9
    Gazzinelli, R. T., Hakim, F. T., Hieny, S., Shearer, G. M. and Sher, A., Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J. Immunol. 1991. 146: 286292.
  • 10
    Suzuki, Y., Sher, A., Yap, G., Park, D., Neyer, L. E., Liesenfeld, O., Fort, M. et al., IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii. J. Immunol. 2000. 164: 53755382.
  • 11
    Aliberti, J., Serhan, C. and Sher, A., Parasite-induced lipoxin A4 is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection. J. Exp. Med. 2002. 196: 12531262.
  • 12
    Hunter, C. A., Villarino, A., Artis, D. and Scott, P., The role of IL-27 in the development of T-cell responses during parasitic infections. Immunol. Rev. 2004. 202: 106114.
  • 13
    Luft, B. J., Kansas, G., Engleman, E. G. and Remington, J. S., Functional and quantitative alterations in T lymphocyte subpopulations in acute toxoplasmosis. J. Infect. Dis. 1984. 150: 761767.
  • 14
    Strickland, G. T., Ahmed, A. and Sell, K. W., Blastogenic response of Toxoplasma-infected mouse spleen cells to T- and B-cell mitogens. Clin. Exp. Immunol. 1975. 22: 167176.
  • 15
    McLeod, R., Eisenhauer, P., Mack, D., Brown, C., Filice, G. and Spitalny, G., Immune responses associated with early survival after peroral infection with Toxoplasma gondii. J. Immunol. 1989. 142: 32473255.
  • 16
    Candolfi, E., Hunter, C. A. and Remington, J. S., Mitogen- and antigen-specific proliferation of T cells in murine toxoplasmosis is inhibited by reactive nitrogen intermediates. Infect. Immun. 1994. 62: 19952001.
  • 17
    Candolfi, E., Hunter, C. A. and Remington, J. S., Roles of gamma interferon and other cytokines in suppression of the spleen cell proliferative response to concanavalin A and toxoplasma antigen during acute toxoplasmosis. Infect. Immun. 1995. 63: 751756.
  • 18
    Channon, J. Y. and Kasper, L. H., Toxoplasma gondii-induced immune suppression by human peripheral blood monocytes: role of gamma interferon. Infect. Immun. 1996. 64: 11811189.
  • 19
    Khan, I. A., Matsuura, T., Fonseka, S. and Kasper, L. H., Production of nitric oxide (NO) is not essential for protection against acute Toxoplasma gondii infection in IRF-1/ mice. J. Immunol. 1996. 156: 636643.
  • 20
    Haque, S., Khan, I., Haque, A. and Kasper, L., Impairment of the cellular immune response in acute murine toxoplasmosis: regulation of interleukin 2 production and macrophage-mediated inhibitory effects. Infect. Immun. 1994. 62: 29082916.
  • 21
    Khan, I. A., Matsuura, T. and Kasper, L. H., IL-10 mediates immunosuppression following primary infection with Toxoplasma gondii in mice. Parasite Immunol. 1995. 17: 185195.
  • 22
    Neyer, L. E., Grunig, G., Fort, M., Remington, J. S., Rennick, D. and Hunter, C. A., Role of interleukin-10 in regulation of T-cell-dependent and T-cell-independent mechanisms of resistance to Toxoplasma gondii. Infect. Immun. 1997. 65: 16751682.
  • 23
    Nie, C. Q., Bernard, N. J., Schofield, L. and Hansen, D. S., CD4+ CD25+ regulatory T cells suppress CD4+ T-cell function and inhibit the development of Plasmodium berghei-specific TH1 responses involved in cerebral malaria pathogenesis. Infect. Immun. 2007. 75: 22752282.
  • 24
    Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. and 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: 11511164.
  • 25
    Takahashi, T., Tagami, T., Yamazaki, S., Uede,T., Shimizu, J., Sakaguchi, N., Mak, T. W. and Sakaguchi, S., Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000. 192: 303310.
  • 26
    Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y., Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 2003. 4: 330336.
  • 27
    Khattri, R., Cox, T., Yasayko, S.A. and Ramsdell, F., An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 2003. 4: 337342.
  • 28
    Sakaguchi, S., Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 2005. 6: 345352.
  • 29
    Belkaid, Y. and Tarbell, K., Regulatory T cells in the control of host-microorganism interactions. Annu. Rev. Immunol. 2009. 27: 551589.
  • 30
    Tenorio, E. P., Olguin, J. E., Fernandez, J., Vieyra, P. and Saavedra, R., Reduction of Foxp3+ cells by depletion with the PC61 mAb induces mortality in resistant BALB/c mice infected with Toxoplasma gondii. J. Biomed. Biotechnol. 2010. DOI: 10.1155/2010/786078.
  • 31
    Oldenhove, G., Bouladoux, N., Wohlfert, E. A., Hall, J. A., Chou, D., Dos, S. L., O'Brien, S. et al., Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity 2009. 31: 772786.
  • 32
    Ge, Y. Y., Zhang, L., Zhang, G., Wu, J. P., Tan, M. J., Hu, E., Liang, Y. J. and Wang, Y., In pregnant mice, the infection of Toxoplasma gondii causes the decrease of CD4+CD25+-regulatory T cells. Parasite Immunol. 2008. 30: 471481.
  • 33
    Khan, I. A., Matsuura, T. and Kasper, L. H., Activation-mediated CD4+ T cell unresponsiveness during acute Toxoplasma gondii infection in mice. Int. Immunol. 1996. 8: 887896.
  • 34
    Sakaguchi, S., Miyara, M., Costantino, C. M. and Hafler, D. A., FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 2010. 10: 490500.
  • 35
    Kuniyasu, Y., Takahashi, T., Itoh, M., Shimizu, J., Toda, G. and Sakaguchi, S., Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. Int. Immunol. 2000. 12: 11451155.
  • 36
    Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y. and Sakaguchi, S., Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 2002. 3: 135142.
  • 37
    Fisson, S., Darrasse-Jeze, G., Litvinova, E., Septier, F., Klatzmann, D., Liblau, R. and Salomon, B. L., Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state. J. Exp. Med. 2003. 198: 737746.
  • 38
    Tenorio, E. P., Fernandez, J., Olguin, J. E. and Saavedra, R., Depletion with PC61 mAb before Toxoplasma gondii infection eliminates mainly Tregs in BALB/c mice but activated cells in C57BL/6J mice. FEMS Immunol. Med. Microbiol. 2011. 62: 362367.
  • 39
    Lyons, A. B., Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J. Immunol. Methods 2000. 243: 147154.
  • 40
    Neyer, L. E., Kang, H., Remington, J. S. and Suzuki, Y., Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to concanavalin-A following peroral infection with Toxoplasma gondii. Parasite Immunol. 1998. 20: 573581.
  • 41
    Thornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y. and Shevach, E. M., Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 2010. 184: 34333441.
  • 42
    Elkord, E., Sharma, S., Burt, D. J. and Hawkins, R. E., Expanded subpopulation of FoxP3(+) T regulatory cells in renal cell carcinoma co-express Helios, indicating they could be derived from natural but not induced Tregs. Clin. Immunol. 2011. 140: 218222.
  • 43
    McClymont, S. A., Putnam, A. L., Lee, M. R., Esensten, J. H., Liu, W., Hulme, M. A., Hoffmuller, U. et al., Plasticity of human regulatory T cells in healthy subjects and patients with type 1 diabetes. J. Immunol. 2011. 186: 39183926.
  • 44
    Fujimoto, M., Nakano, M., Terabe, F., Kawahata, H., Ohkawara, T., Han, Y., Ripley, B. et al., The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells. J. Immunol. 2011. 186: 3240.
  • 45
    Verhagen, J. and Wraith, D. C., Comment on “Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells”. J. Immunol. 2010. 185: 7129.
  • 46
    Vigario, A. M., Gorgette, O., Dujardin, H. C., Cruz, T., Cazenave, P. A., Six, A., Bandeira, A. and Pied, S., Regulatory CD4+ CD25+ Foxp3+ T cells expand during experimental Plasmodium infection but do not prevent cerebral malaria. Int. J. Parasitol. 2007. 37: 963973.
  • 47
    McSorley, H. J., Harcus, Y. M., Murray, J., Taylor, M.D. and Maizels, R. M., Expansion of Foxp3+ regulatory T cells in mice infected with the filarial parasite Brugia malayi. J. Immunol. 2008. 181: 64566466.
  • 48
    Rausch, S., Huehn, J., Kirchhoff, D., Rzepecka, J., Schnoeller, C., Pillai, S., Loddenkemper, C. et al., Functional analysis of effector and regulatory T cells in a parasitic nematode infection. Infect. Immun. 2008. 76: 19081919.
  • 49
    Taylor, M. D., van der, W. N., Harris, A., Graham, A. L., Bain, O., Allen, J. E. and Maizels, R. M., Early recruitment of natural CD4+ Foxp3+ Treg cells by infective larvae determines the outcome of filarial infection. Eur. J. Immunol. 2009. 39: 192206.
  • 50
    Finney, C. A., Taylor, M. D., Wilson, M. S. and Maizels, R. M., Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection. Eur. J. Immunol. 2007. 37: 18741886.
  • 51
    Jankovic, D., Kullberg, M. C., Feng, C. G., Goldszmid, R. S., Collazo, C. M., Wilson, M., Wynn, T. A. et al., Conventional T-bet(+)Foxp3(−) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J. Exp. Med. 2007. 204: 273283.
  • 52
    de la Rosa, M., Rutz, S., Dorninger, H. and Scheffold, A., Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur. J. Immunol. 2004. 34: 24802488.
  • 53
    Pandiyan, P., Zheng, L., Ishihara, S., Reed, J. and Lenardo, M. J., CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat. Immunol. 2007. 8: 13531362.
  • 54
    Scheffold, A., Huhn, J. and Hofer, T., Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur. J. Immunol. 2005. 35: 13361341.
  • 55
    Sakaguchi, S., Miyara, M., Costantino, C. M. and Hafler, D. A., FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 2010. 10: 490500.
  • 56
    Busse, D., de la Rosa, M., Hobiger, K., Thurley, K., Flossdorf, M., Scheffold, A. and Hofer, T., Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proc. Natl. Acad. Sci. USA 2010. 107: 30583063.
  • 57
    Sharma, S. D., Hofflin, J. M. and Remington, J. S., In vivo recombinant interleukin 2 administration enhances survival against a lethal challenge with Toxoplasma gondii. J. Immunol. 1985. 135: 41604163.
  • 58
    Wojno, E. D., Hosken, N., Stumhofer, J. S., O'Hara, A. C., Mauldin, E., Fang, Q., Turka, L. A. et al., A role for IL-27 in limiting T regulatory cell populations. J. Immunol. 2011. 187: 266273.
  • 59
    Villarino, A. V., Stumhofer, J. S., Saris, C. J., Kastelein, R. A., de Sauvage, F. J. and Hunter, C. A., IL-27 limits IL-2 production during Th1 differentiation. J. Immunol. 2006. 176: 237247.
  • 60
    Malek, T. R., The biology of interleukin-2. Annu. Rev. Immunol. 2008. 26: 453479.
  • 61
    Piña-Vazquez, C., Saavedra, R. and Herion, P., A quantitative competitive PCR method to determine the parasite load in the brain of Toxoplasma gondii-infected mice. Parasitol. Int. 2008. 57: 347353.
  • 62
    Tenorio, E. P. and Saavedra, R., Differential effect of sodium arsenite during the activation of human CD4+ and CD8+ T lymphocytes. Int. Immunopharmacol. 2005. 5: 18531869.
  • 63
    Montes, M., Jaensson, E. A., Orozco, A. F., Lewis, D. E. and Corry, D. B., A general method for bead-enhanced quantitation by flow cytometry. J. Immunol. Methods 2006. 317: 4555.
  • 64
    Foster, B., Prussin, C., Liu, F., Whitmire, J. K. and Whitton, J. L., Detection of intracellular cytokines by flow cytometry. Curr. Protoc. Immunol. 2007. 6.24.1–6.24.21.