title: Resistance of regulatory T cells to glucocorticoid-induced [corrected] TNFR family-related protein (GITR) during Plasmodium yoelii infection.
abstract: CD4+ T cells are the major effector T cells against blood-stage Plasmodium yoelii infection. On the other hand, the lethal strain of P. yoelii (PyL) has acquired an escape mechanism from host T cell immunity by activating CD4+CD25+ regulatory T cells (Treg). Although the activation of Treg during PyL infection precludes the clearance of PyL from mice, it remains unclear whether activation of Treg is attributable to a specific response against PyL infection. Thus, we examined here whether Treg proliferate in an antigen-dependent manner during PyL infection. We also investigated the effector and regulatory mechanisms of Treg. Infection with PyL increased the number of CD4+CD25+ T cells, in which expression of Foxp3 mRNA is up-regulated. The Treg that were transferred into mice infected with PyL, but not with a non-lethal strain of P. yoelii (PyNL), proliferated during the initial 5 days following infection. The Treg from PyL-infected mice showed strong suppression compared with those from naive or PyNL-infected mice, and could suppress T cell activation by recognizing PyL- but not PyNL-derived antigens. Furthermore, the suppressive function of Treg activated in PyL-infected but not in naive mice could not be inhibited by treatment with an anti-glucocorticoid-induced TNFR family-related protein (GITR) mAb. These findings indicate that PyL infection specifically activates Treg that are specific for PyL-derived antigens. The infection also induces resistance for Treg to GITR signaling, and this eventually contributes to the escape of parasites from host T cell immunity.
authors.affiliation: Department of Immunology & Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hamano
authors.forename: Chikage
authors.initials: C
authors.lastname: Mitoma-Obata
authors.forename: Kohhei
authors.initials: K
authors.lastname: Tetsutani
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Himeno
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000913:Antibodies, Protozoan / Q000494:pharmacology; D005260:Female; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007113:Immunity, Innate; D008288:Malaria / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity; D017475:Receptors, Nerve Growth Factor / Q000276:immunology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000502:physiology*; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D053450:Glucocorticoid-Induced TNFR-Related Protein; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C106544:Tnfrsf18 protein, mouse