• 1
    Maizels, R. M. and Yazdanbakhsh, M., Regulation of the immune response by helminth parasites: Cellular and molecular mechanisms. Nat. Rev. Immunol. 2003. 3: 733743.
  • 2
    Mountford, A. P. and Trottein, F., Schistosomes in the skin: A balance between immune priming and regulation. Trends Parasitol. 2004. 20: 221226.
  • 3
    Harnett, W., Goodridge, H. S. and Harnett, M. M., Subversion of immune cell signal transduction pathways by the secreted filarial nematode product, ES-62. Parasitology 2005. 130 Suppl: S63S68.
  • 4
    Smith, P., Fallon, R. E., Mangan, N. E., Walsh, C. M., Saraiva, M., Sayers, J. R., McKenzie, A. N. J. et al., Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity. J. Exp. Med. 2005. 202: 13191325.
  • 5
    Maizels, R. M., Balic, A., Gomez-Escobar, N., Nair, M., Taylor, M. and Allen, J. E., Helminth parasites: Masters of regulation. Immunol. Rev. 2004. 201: 89116.
  • 6
    Taylor, M., Le Goff, L., Harris, A., Malone, E., Allen, J. E. and Maizels, R. M., Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo. J. Immunol. 2005. 174: 49244933.
  • 7
    Wynn, T. A., Thompson, R. W., Cheever, A. W. and Mentink-Kane, M. M., Immunopathogenesis of schistosomiasis. Immunol. Rev. 2004. 201: 156167.
  • 8
    Wynn, T. A., Cheever, A. W., Williams, M. E., Hieny, S., Caspar, P., Kühn, R., Müller, W. and Sher, A., IL-10 regulates liver pathology in acute murine schistosomiasis mansoni but is not required for immune down-modulation of chronic disease. J. Immunol. 1998. 159: 44734480.
  • 9
    Singh, K. P., Gerard, H. C., Hudson, A. P., Reddy, T. R. and Boros, D. L., Retroviral Foxp3 gene transfer ameliorates liver granuloma pathology in Schistosoma mansoni infected mice. Immunology 2005. 114: 410417.
  • 10
    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.
  • 11
    Hori, S., Nomura, T. and Sakaguchi, S., Control of regulatory T cell development by the transcription factor Foxp3. Science 2003. 299: 10571061.
  • 12
    Jarrett, E. E. E. and Stewart, D. C., Potentiation of rat reagenic (IgE) antibody by helminth infection. Simultaneous potentiation of separate reagins. Immunology 1972. 23: 749755.
  • 13
    Kullberg, M. C., Pearce, E. J., Hieny, S. E., Sher, A. and Berzofsky, J. A., Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen. J. Immunol. 1992. 148: 32643270.
  • 14
    Cooke, A., Tonks, P., Jones, F. M., O'Shea, H., Hutchings, P., Fulford, A. J. and Dunne, D. W., Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999. 21: 169176.
  • 15
    La Flamme, A. C., Ruddenklau, K. and Backstrom, B. T., Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect. Immun. 2003. 71: 49965004.
  • 16
    Wang, C. C., Nolan, T. J., Schad, G. A. and Abraham, D., Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin. Exp. Allergy 2001. 31: 495503.
  • 17
    Wilson, M. S., Taylor, M., Balic, A., Finney, C. A. M., Lamb, J. R. and Maizels, R. M., Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J. Exp. Med. 2005. 202: 11991212.
  • 18
    Urban, J. F., Jr., Katona, I. M., Paul, W. E. and Finkelman, F. D., Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc. Natl. Acad. Sci. USA 1991. 88: 55135517.
  • 19
    Svetic, A., Madden, K. B., di Zhou, X., Lu, P., Katona, I. M., Finkelman, F. D., Urban, J. F., Jr. and Gause, W. C., A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3. J. Immunol. 1993. 150: 34343441.
  • 20
    Wahid, F. N., Behnke, J. M., Grencis, R. K., Else, K. J. and Ben-Smith, A. W., Immunological relationships during primary infection with Heligmosomoides polygyrus: Th2 cytokines and primary response phenotype. Parasitology 1994. 108: 461471.
  • 21
    Shi, H. N., Ingui, C. J., Dodge, I. and Nagler-Anderson, C., A helminth-induced mucosal Th2 response alters nonresponsiveness to oral administration of a soluble antigen. J. Immunol. 1998. 160: 24492455.
  • 22
    Finkelman, F. D., Morris, S. C., Orekhova, T., Mori, M., Donaldson, D., Reiner, S. L., Reilly, N. L. et al., STAT6 regulation of in vivo IL-4 responses. J. Immunol. 2000. 164: 23032310.
  • 23
    Mohrs, K., Harris, D. P., Lund, F. E. and Mohrs, M., Systemic dissemination and persistence of Th2 and type 2 cells in response to infection with a strictly enteric nematode parasite. J. Immunol. 2005. 175: 53065313.
  • 24
    Fox, J. G., Beck, P., Dangler, C. A., Whary, M. T., Wang, T. C., Shi, H. N. and Nagler-Anderson, C., Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy. Nat. Med. 2000. 6: 536542.
  • 25
    Bashir, M. E., Andersen, P., Fuss, I. J., Shi, H. N. and Nagler-Anderson, C., An enteric helminth infection protects against an allergic response to dietary antigen. J. Immunol. 2002. 169: 32843292.
  • 26
    Elliott, D. E., Setiawan, T., Metwali, A., Blum, A., Urban, J. F., Jr. and Weinstock, J. V., Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur. J. Immunol. 2004. 34: 26902698.
  • 27
    Monroy, F. G. and Enriquez, F. J., Heligmosomoides polygyrus: A model for chronic gastrointestinal helminthiasis. Parasitol. Today 1992. 8: 4954.
  • 28
    Behnke, J. M. and Parish, H. A., Nematospiroides dubius: Arrested development of larvae in immune mice. Exp. Parasitol. 1979. 47: 116127.
  • 29
    Behnke, J. M., Evasion of immunity by nematode parasites causing chronic infections. Adv. Parasitol. 1987. 26: 171.
  • 30
    Pritchard, D. I., Williams, D. J. L., Behnke, J. M. and Lee, T. D. G., The role of IgG1 hypergammaglobulinaemia in immunity to the gastrointestinal nematode Nematospiroides dubius. The immunochemical purification, antigen-specificity and in vivo anti-parasite effect of IgG1 from immune serum. Immunology 1983. 49: 353365.
  • 31
    Su, Z., Segura, M., Morgan, K., Loredo-Osti, J. C. and Stevenson, M. M., Impairment of protective immunity to blood-stage malaria by concurrent nematode infection. Infect. Immun. 2005. 73: 35313539.
  • 32
    Shevach, E. M., CD4+ CD25+ suppressor T cells: More questions than answers. Nat. Rev. Immunol. 2002. 2: 389400.
  • 33
    Thornton, A. M. and Shevach, E. M., CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998. 188: 287296.
  • 34
    Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J. L., Farr, A. G. and Rudensky, A. Y., Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 2005. 22: 329341.
  • 35
    Tang, Q., Boden, E. K., Henriksen, K. J., Bour-Jordan, H., Bi, M. and Bluestone, J. A., Distinct roles of CTLA-4 and TGF-β in CD4+CD25+ regulatory T cell function. Eur. J. Immunol. 2004. 34: 29963005.
  • 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
    Maloy, K. J. and Powrie, F., Regulatory T cells in the control of immune pathology. Nat. Immunol. 2001. 2: 816822.
  • 38
    Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M. and Sacks, D. L., CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002. 420: 502507.
  • 39
    Suvas, S., Kumaraguru, U., Pack, C. D., Lee, S. and Rouse, B. T., CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J. Exp. Med. 2003. 198: 889901.
  • 40
    Mills, K. H. G., Regulatory T cells: Friend or foe in immunity to infection? Nat. Rev. Immunol. 2004. 4: 841855.
  • 41
    Belkaid, Y. and Rouse, B. T., Natural regulatory T cells in infectious disease. Nat. Immunol. 2005. 6: 353360.
  • 42
    Hisaeda, H., Maekawa, Y., Iwakawa, D., Okada, H., Himeno, K., Kishihara, K., Tsukumo, S.-I. and Yasutomo, K., Escape of malaria parasites from host immunity requires CD4+CD25+ regulatory T cells. Nat. Med. 2004. 10: 2930.
  • 43
    Kullberg, M. C., Jankovic, D., Gorelick, P. L., Caspar, P., Letterio, J. J., Cheever, A. W. and Sher, A., Bacteria-triggered CD4+ T regulatory cells suppress Helicobacter hepaticus-induced colitis. J. Exp. Med. 2002. 196: 505515.
  • 44
    Raghavan, S., Fredriksson, M., Svennerholm, A. M., Holmgren, J. and 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. 2003. 132: 393400.
  • 45
    Hesse, M., Piccirillo, C. A., Belkaid, Y., Prufer, J., Mentink-Kane, M., Leusink, M., Cheever, A. W. et al., The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing innate effector and regulatory T cells. J. Immunol. 2004. 172: 31573166.
  • 46
    King, C. L., Mahanty, S., Kumaraswami, V., Abrams, J. S., Regunathan, J., Jayaraman, K., Ottesen, E. A. and Nutman, T. B., Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J. Clin. Invest. 1993. 92: 16671673.
  • 47
    Hoerauf, A. and Brattig, N., Resistance and susceptibility in human onchocerciasis – beyond Th1 vs. Th2. Trends Parasitol. 2002. 18: 2531.
  • 48
    Steel, C. and Nutman, T. B., CTLA-4 in filarial infections: Implications for a role in diminished T cell reactivity. J. Immunol. 2003. 170: 19301938.
  • 49
    Babu, S., Blauvelt, C. P., Kumaraswami, V. and Nutman, T. B., Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: Implications for parasite persistence. J. Immunol. 2006. 176: 32483256.
  • 50
    Gillan, V. and Devaney, E., Regulatory T cells modulate Th2 responses induced by Brugia pahangi third-stage larvae. Infect. Immun. 2005. 73: 40344042.
  • 51
    Baumgart, M., Tomkins, F., Leng, J. and Hesse, M., Naturally-occurring CD4+Foxp3+ regulatory T cells are an essential, IL-10-independent part of the immunoregulatory network in Schistosoma mansoni egg-induced inflammation. J. Immunol. 2006. 176: 53745387.
  • 52
    Taylor, J. J., Mohrs, M. and Pearce, E. J., Regulatory T cell responses develop in parallel to Th responses, and control the magnitude and phenotype of the Th effector population. J. Immunol. 2006. 176: 58395847.
  • 53
    McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M. and Byrne, M. C., CD4+CD25+ immunoregulatory T cells: Gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002. 16: 311323.
  • 54
    Bluestone, J. A. and Abbas, A. K., Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 2003. 3: 253257.
  • 55
    Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., de Vries, J. E. and Roncarolo, M. G., A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997. 389: 737742.
  • 56
    Chen, Y., Kuchroo, V. K., Inobe, J.-I., Hafler, D. A. and Weiner, H. L., Regulatory T cell clones induced by oral tolerance: Suppression of autoimmune encephalomyelitis. Science 1994. 265: 12371240.
  • 57
    Vieira, P. L., Christensen, J. R., Minaee, S., O'Neill, E. J., Barrat, F. J., Boonstra, A., Barthlott, T. et al., IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J. Immunol. 2004. 172: 59865993.
  • 58
    Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G. and Wahl, S. M., Conversion of peripheral CD4+CD25 naïve T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med. 2003. 198: 18751886.
  • 59
    Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R. and Neurath, M. F., TGF-β induces a regulatory phenotype in CD4+CD25 T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 2004. 172: 51495153.
  • 60
    Wan, Y. Y. and Flavell, R. A., Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc. Natl. Acad. Sci. USA 2005. 102: 51265131.
  • 61
    Knoechel, B., Lohr, J., Kahn, E., Bluestone, J. A. and Abbas, A. K., Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J. Exp. Med. 2005. 202: 13751386.
  • 62
    Helmby, H. and Grencis, R. K., Contrasting roles for IL-10 in protective immunity to different life cycle stages of intestinal nematode parasites. Eur. J. Immunol. 2003. 33: 23822390.
  • 63
    Green, E. A., Gorelik, L., McGregor, C. M., Tran, E. H. and Flavell, R. A., CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-β-TGF-β receptor interactions in type 1 diabetes. Proc. Natl. Acad. Sci. USA 2003. 100: 1087810883.
  • 64
    Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. and Flavell, R. A., Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunol. 2006. 24: 99146.
  • 65
    Doligalska, M., Rzepecka, J., Drela, N., Donskow, K. and Gerwel-Wronka, M., The role of TGF-β in mice infected with Heligmosomoides polygyrus. Parasite Immunol. 2006. 28: 387395.
  • 66
    Egen, J. G., Kuhns, M. S. and Allison, J. P., CTLA-4: New insights into its biological function and use in tumor immunotherapy. Nat. Immunol. 2002. 3: 611618.
  • 67
    McCoy, K., Camberis, M. and Le Gros, G., Protective immunity to nematode infection is induced by CTLA-4 blockade. J. Exp. Med. 1997. 186: 183187.
  • 68
    Huehn, J. and Hamann, A., Homing to suppress: Address codes for Treg migration. Trends Immunol. 2005. 26: 632636.
  • 69
    Siegmund, K., Feuerer, M., Siewert, C., Ghani, S., Haubold, U., Dankof, A., Krenn, V. et al., Migration matters: Regulatory T-cell compartmentalization determines suppressive activity in vivo. Blood 2005. 106: 30973104.
  • 70
    Suffia, I., Reckling, S. K., Salay, G. and Belkaid, Y., A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania major infection. J. Immunol. 2005. 174: 54445455.
  • 71
    Robinson, P. W., Green, S. J., Carter, C., Coadwell, J. and Kilshaw, P. J., Studies on transcriptional regulation of the mucosal T-cell integrin αEβ7 (CD103). Immunology 2001. 103: 146154.