title: Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner.
abstract: Th17 cells and Foxp3+ regulatory T cells (Tregs) are thought to promote and suppress inflammatory responses, respectively. However, whether they counteract each other or synergize in regulating immune reactions remains controversial. To determine their interactions, we describe the results of experiments employing mouse models of intestinal inflammation by transferring antigen-specific Th cells (Th1, Th2, and Th17) differentiated in vitro followed by the administration of the cognate antigen via enema. We show that cotransfer of induced Tregs (iTregs) suppressed Th1- and Th2-mediated colon inflammation. In contrast, colon inflammation induced by transfer of Th17 cells, was augmented by the cotransfer of iTregs. Furthermore, oral delivery of antigen potentiated Th17-mediated colon inflammation. Administration of a blocking antibody against cytotoxic T lymphocyte-associated antigen 4 (CTLA4) abrogated the effects of cotransfer of iTregs, while the injection of a soluble recombinant immunoglobulin (Ig) fusion protein, CTLA4-Ig substituted for the cotransfer of iTregs. These results suggest that antigen-specific activation of iTregs in a local environment stimulates the Th17-mediated inflammatory response in a CTLA4-dependent manner.
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaminuma
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
mesh_terms: D000069594:Abatacept / Q000276:immunology; D000818:Animals; D060908:CTLA-4 Antigen / Q000378:metabolism*; D003106:Colon / Q000276:immunology* / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D000069594:Abatacept; D010047:Ovalbumin