• 1
    Ottesen, E. A., Weller, P. F. and Heck, L., Specific cellular immune unresponsiveness in human filariasis. Immunology 1977. 33: 413421.
  • 2
    Piessens, W. F., McGreevy, P. B., Piessens, P. W., McGreevy, M., Koiman, I., Saroso, J. S. and Dennis, D. T., Immune responses in human infections with Brugia malayi. Specific cellular unresponsiveness to filarial antigens. J. Clin. Invest. 1980. 65: 172179.
  • 3
    King, C. L., Kumaraswami, V., Poindexter, R. W., Kumari, S., Jayaraman, K., Alling, D. W., Ottesen, E. A. and Nutman, T. B., Immunologic tolerance in lymphatic filariasis. Diminished parasite-specific T and B cell lymphocyte precursor frequency in the microfilaremic state. J. Clin. Invest. 1992. 89: 14031410.
  • 4
    Grogan, J. L., Kremsner, P. G., Deelder, A. M. and Yazdanbakhsh, M., Antigen-specific proliferation and interferon-gamma and interleukin-5 production are down-regulated during Schistosoma haematobium infection. J. Infect. Dis. 1998. 177: 14331437.
  • 5
    Maizels, R. M., Balic, A., Gomez-Escobar, N., Nair, M., Taylor, M. D. and Allen, J. E., Helminth parasites–masters of regulation. Immunol. Rev. 2004. 201: 89116.
  • 6
    van Riet, E., Hartgers, F. C. and Yazdanbakhsh, M., Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 2007. 212: 475490.
  • 7
    Hoerauf, A., Satoguina, J., Saeftel, M. and Specht, S., Immunomodulation by filarial nematodes. Parasite Immunol. 2005. 27: 417429.
  • 8
    Sartono, E., Kruize, Y. C. M., Kurniawan-Atmadja, A., Maizels, R. M. and Yazdanbakhsh, M., Depression of antigen-specific interleukin-5 and interferon-g responses in human lymphatic filariasis as a function of clinical status and age. J. Infect. Dis. 1997. 175: 12761280.
  • 9
    Steel, C. and Nutman, T. B., Regulation of IL-5 in onchocerciasis. A critical role for IL-2. J. Immunol. 1993. 150: 55115518.
  • 10
    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.
  • 11
    Cooper, P. J., Mancero, T., Espinel, M., Sandoval, C., Lovato, R., Guderian, R. H. and Nutman, T. B., Early human infection with Onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response. J. Infect. Dis. 2001. 183: 16621668.
  • 12
    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.
  • 13
    Roncarolo, M. G., Gregori, S., Battaglia, M., Bacchetta, R., Fleischhauer, K. and Levings, M. K., Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 2006. 212: 2850.
  • 14
    Fahlen, L., Read, S., Gorelik, L., Hurst, S. D., Coffman, R. L., Flavell, R. A. and Powrie, F., T cells that cannot respond to TGF-β escape control by CD4+CD25+ regulatory T cells. J. Exp. Med. 2005. 201: 737746.
  • 15
    Marie, J. C., Letterio, J. J., Gavin, M. and Rudensky, A. Y., TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 2005. 201: 10611067.
  • 16
    Sun, C. M., Hall, J. A., Blank, R. B., Bouladoux, N., Oukka, M., Mora, J. R. and Belkaid, Y., Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 Treg cells via retinoic acid. J. Exp. Med. 2007. 204: 17751785.
  • 17
    Fantini, M. C., Becker, C., Monteleone, G., Pallone, F., Galle, P. R. and Neurath, M. F., Cutting edge: TGF-β induces a regulatory phenotype in CD4+CD25 T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 2004. 172: 51495153.
  • 18
    Coombes, J. L., Siddiqui, K. R., Arancibia-Carcamo, C. V., Hall, J., Sun, C. M., Belkaid, Y. and Powrie, F., A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J. Exp. Med. 2007. 204: 17571764.
  • 19
    Doetze, A., Satoguina, J., Burchard, G., Rau, T., Loliger, C., Fleischer, B. and Hoerauf, A., Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T(h)3/T(r)1-type cytokines IL-10 and transforming growth factor-beta but not by a T(h)1 to T(h)2 shift. Int. Immunol. 2000. 12: 623630.
  • 20
    Korten, S., Badusche, M., Buttner, D. W., Hoerauf, A., Brattig, N. and Fleischer, B., Natural death of adult Onchocerca volvulus and filaricidal effects of doxycycline induce local FOXP3+/CD4+ regulatory T cells and granzyme expression. Microb. Infect. 2008. 10: 313324.
  • 21
    Satoguina, J., Mempel, M., Larbi, J., Badusche, M., Loliger, C., Adjei, O., Gachelin, G. et al., Antigen-specific T regulatory-1 cells are associated with immunosuppression in a chronic helminth infection (onchocerciasis). Microb. Infect. 2002. 4: 12911300.
  • 22
    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.
  • 23
    Taylor, M. D., Harris, A., Babayan, S. A., Bain, O., Culshaw, A., Allen, J. E. and Maizels, R. M., CTLA-4 and CD4+CD25+ regulatory T cells inhibit protective immunity to filarial parasites in vivo. J. Immunol. 2007. 179: 46264634.
  • 24
    Beiting, D. P., Gagliardo, L. F., Hesse, M., Bliss, S. K., Meskill, D. and Appleton, J. A., Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-β. J. Immunol. 2007. 178: 10391047.
  • 25
    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.
  • 26
    Wilson, M. S., Taylor, M. D., Balic, A., Finney, C. A., Lamb, J. R. and Maizels, R. M., Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J. Exp. Med. 2005. 202: 11991212.
  • 27
    Metwali, A., Setiawan, T., Blum, A. M., Urban, J., Elliott, D. E., Hang, L. and Weinstock, J. V., Induction of CD8+ regulatory T cells in the intestine by Heligmosomoides polygyrus infection. Am. J. Physiol. Gastrointest. Liver Physiol. 2006. 291: G253G259.
  • 28
    Freeman, C. M., Chiu, B. C., Stolberg, V. R., Hu, J., Zeibecoglou, K., Lukacs, N. W., Lira, S. A. et al., CCR8 is expressed by antigen-elicited, IL-10-producing CD4+CD25+ T cells, which regulate Th2-mediated granuloma formation in mice. J. Immunol. 2005. 174: 19621970.
  • 29
    van der Kleij, D., Latz, E., Brouwers, J. F., Kruize, Y. C., Schmitz, M., Kurt-Jones, E. A., Espevik, T. et al., A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. J. Biol. Chem. 2002. 277: 4812248129.
  • 30
    Watanabe, K., Mwinzi, P. N., Black, C. L., Muok, E. M., Karanja, D. M., Secor, W. E. and Colley, D. G., T regulatory cell levels decrease in people infected with Schistosoma mansoni on effective treatment. Am. J. Trop. Med. Hyg. 2007. 77: 676682.
  • 31
    Baumgart, M., Tompkins, 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.
  • 32
    Layland, L. E., Rad, R., Wagner, H. and da Costa, C. U., Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2. Eur. J. Immunol. 2007. 37: 21742184.
  • 33
    McKee, A. S. and Pearce, E. J., CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. J. Immunol. 2004. 173: 12241231.
  • 34
    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. Immunol. 2005. 114: 410417.
  • 35
    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.
  • 36
    Smith, P., Mangan, N. E., Walsh, C. M., Fallon, R. E., McKenzie, A. N., van Rooijen, N. and Fallon, P. G., Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J. Immunol. 2007. 178: 45574566.
  • 37
    Sakaguchi, S., Ono, M., Setoguchi, R., Yagi, H., Hori, S., Fehervari, Z., Shimizu, J. et al., Foxp3+ CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol. Rev. 2006. 212: 827.
  • 38
    Belkaid, Y., Regulatory T cells and infection: a dangerous necessity. Nat. Rev. Immunol. 2007. 7: 875888.
  • 39
    Mills, K. H., Regulatory T cells: friend or foe in immunity to infection? Nat. Rev. Immunol. 2004. 4: 841855.
  • 40
    Zheng, Y. and Rudensky, A. Y., Foxp3 in control of the regulatory T cell lineage. Nat. Immunol. 2007. 8: 457462.
  • 41
    Jordan, M. S., Boesteanu, A., Reed, A. J., Petrone, A. L., Holenbeck, A. E., Lerman, M. A., Naji, A. and Caton, A. J., Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2001. 2: 301306.
  • 42
    Dittrich, A. M., Erbacher, A., Specht, S., Diesner, F., Krokowski, M., Avagyan, A. and Stock, P., Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J. Immunol. 2008. 180: 17921799.
  • 43
    Smits, H. H., Hammad, H., van Nimwegen, M., Soullie, T., Willart, M. A., Lievers, E. and Kadouch, J., Protective effect of Schistosoma mansoni infection on allergic airway inflammation depends on the intensity and chronicity of infection. J. Allergy Clin. Immunol. 2007. 120: 932940.
  • 44
    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.
  • 45
    Freitas, T. C., Jung, E. and Pearce, E. J., TGF-β signaling controls embryo development in the parasitic flatworm Schistosoma mansoni. PLoS Pathog. 2007. 3: e52.
  • 46
    Gomez-Escobar, N., Gregory, W. F. and Maizels, R. M., Identification of tgh-2, a filarial nematode homolog of Caenorhabditis elegans daf-7 and human transforming growth factor beta, expressed in microfilarial and adult stages of Brugia malayi. Infect. Immun. 2000. 68: 64026410.
  • 47
    Maizels, R. M., Gomez-Escobar, N., Gregory, W. F., Murray, J. and Zang, X., Immune evasion genes from filarial nematodes. Int. J. Parasitol. 2001. 31: 889898.
  • 48
    Hoffmann, W. H., Petit, G., Schulz-Key, H., Taylor, D. W., Bain, O. and Le Goff, L., Litomosoides sigmodontis in mice: reappraisal of an old model for filarial research. Parasitol. Today 2000. 16: 387389.
  • 49
    Petit, G., Diagne, M., Maréchal, P., Owen, D., Taylor, D. and Bain, O., Maturation of the filaria Litomosoides sigmodontis in BALB/c mice; comparative susceptibility of nine other inbred strains. Ann. Parasitol. Hum. Comp. 1992. 67: 144150.
  • 50
    Taylor, M. D., LeGoff, 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.
  • 51
    Specht, S., Volkmann, L., Wynn, T. and Hoerauf, A., Interleukin-10 (IL-10) counterregulates IL-4-dependent effector mechanisms in Murine Filariasis. Infect. Immun. 2004. 72: 62876293.
  • 52
    Babayan, S., Ungeheuer, M. N., Martin, C., Attout, T., Belnoue, E., Snounou, G., Renia, L. et al., Resistance and susceptibility to filarial infection with Litomosoides sigmodontis are associated with early differences in parasite development and in localized immune reactions. Infect. Immun. 2003. 71: 68206829.
  • 53
    Stephens, L. A. and Anderton, S. M., Comment on “Cutting edge: anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells”. J. Immunol. 2006. 177: 2036
  • 54
    Couper, K. N., Blount, D. G., de Souza, J. B., Suffia, I., Belkaid, Y. and Riley, E. M., Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice. J. Immunol. 2007. 178: 41364146.
  • 55
    Kohm, A. P., McMahon, J. S., Podojil, J. R., Begolka, W. S., DeGutes, M., Kasprowicz, D. J., Ziegler, S. F. and Miller, S. D., Cutting Edge: Anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J. Immunol. 2006. 176: 33013305.
  • 56
    Zelenay, S. and Demengeot, J., Comment on “Cutting edge: anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells”. J. Immunol. 2006. 177: 20362037.
  • 57
    Fecci, P. E., Sweeney, A. E., Grossi, P. M., Nair, S. K., Learn, C. A., Mitchell, D. A., Cui, X. et al., Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells. Clin. Canc. Res. 2006. 12: 42944305.
  • 58
    Graham, A. L., Taylor, M. D., Le Goff, L., Lamb, T. J., Magennis, M. and Allen, J. E., Quantitative appraisal of murine filariasis confirms host strain differences but reveals that BALB/c females are more susceptible than males to Litomosoides sigmodontis. Microb. Infect. 2005. 7: 612618.
  • 59
    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.
  • 60
    Mendez, S., Reckling, S. K., Piccirillo, C. A., Sacks, D. and Belkaid, Y., Role for CD4+CD25+ regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J. Exp. Med. 2004. 200: 201210.
  • 61
    Agnew, A., Murare, H. M. and Doenhoff, M. J., Immune attrition of adult schistosomes. Parasite Immunol. 1993. 15: 261271.
  • 62
    Urban, J. F., Jr., Katona, I. M. and Finkelman, F. D., Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice. Exp. Parasitol. 1991. 73: 500511.
  • 63
    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.
  • 64
    Devaney, E., Gillan, V., Wheatley, I., Jenson, J., O'Connor, R. and Balmer, P., Interleukin-4 influences the production of microfilariae in a mouse model of Brugia infection. Parasite Immunol. 2002. 24: 2937.
  • 65
    Volkmann, L., Saeftel, M., Bain, O., Fischer, K., Fleischer, B. and Hoerauf, A., Interleukin-4 is essential for the control of microfilariae in murine infection with the filaria Litomosoides sigmodontis. Infect. Immun. 2001. 69: 29502956.
  • 66
    Behnke, J. M. and Parish, H. A., Expulsion of Nematospiroides dubius from the intestine of mice treated with immune serum. Parasite Immunol. 1979. 1: 1326.
  • 67
    Liu, S. X., Song, G. C., Xu, Y. X. and McManus, D. P., Anti-fecundity immunity induced in pigs vaccinated with recombinant Schistosoma japonicum 26 kDa glutathione transferase. Parasite Immunol. 1995. 17: 335340.
  • 68
    Loukas, A., Bethony, J. M., Williamson, A. L., Goud, G. N., Mendez, S., Zhan, B., Hawdon, J. M. et al., Vaccination of dogs with a recombinant cysteine protease from the intestine of canine hookworms diminishes the fecundity and growth of worms. J. Infect. Dis. 2004. 189: 19521961.
  • 69
    Semnani, R. T., Law, M., Kubofcik, J. and Nutman, T. B., Filaria-induced immune evasion: suppression by the infective stage of Brugia malayi at the earliest host-parasite interface. J. Immunol. 2004. 172: 62296238.
  • 70
    Semnani, R. T. and Nutman, T. B., Toward an understanding of the interaction between filarial parasites and host antigen-presenting cells. Immunol. Rev. 2004. 201: 127138.
  • 71
    Taylor, M. D., Harris, A., Nair, M. G., Maizels, R. M. and Allen, J. E., F4/80+ alternatively activated macrophages control CD4+ T cell hyporesponsiveness at sites peripheral to filarial infection. J. Immunol. 2006. 176: 69186927.
  • 72
    MacDonald, A. S., Maizels, R. M., Lawrence, R. A., Dransfield, I. and Allen, J. E., Requirement for in vivo production of IL-4, but not IL-10, in the induction of proliferative suppression by filarial parasites. J. Immunol. 1998. 160: 41244132.
  • 73
    Harnett, W. and Harnett, M. M., Molecular basis of worm-induced immunomodulation. Parasite Immunol. 2006. 28: 535543.
  • 74
    Gillan, V. and Devaney, E., Regulatory T cells modulate Th2 responses induced by Brugia pahangi third-stage larvae. Infect. Immun. 2005. 73: 40344042.
  • 75
    Stephens, G. L., McHugh, R. S., Whitters, M. J., Young, D. A., Luxenberg, D., Carreno, B. M., Collins, M. and Shevach, E. M., Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J. Immunol. 2004. 173: 50085020.
  • 76
    Ji, H. B., Liao, G., Faubion, W. A., Abadia-Molina, A. C., Cozzo, C., Laroux, F. S., Caton, A. and Terhorst, C., Cutting edge: the natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression. J. Immunol. 2004. 172: 58235827.
  • 77
    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.
  • 78
    Fathman, C. G. and Lineberry, N. B., Molecular mechanisms of CD4+ T-cell anergy. Nat. Rev. Immunol. 2007. 7: 599609.
  • 79
    Breton, B., Diagne, M., Wanji, S., Bougnoux, M. E., Chandre, F., Marechal, P., Petit, G. et al., Ivermectin and moxidectin in two filarial systems: resistance of Monanema martini; inhibition of Litomosoides sigmodontis insemination. Parassitologia 1997. 39: 1928.