Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
In animals with transplant tolerance without lympho-hemopoietic chimerism peripheral T cells reactive to donor are not deleted, but their capacity to effect rejection is inhibited by alloantigen specific CD4+CD25+T regulatory cells. Detection of tolerance by in vitro assays has not been established.
Here we compared the proliferation of CD4+, CD4+CD25+ and CD4+CD25– T cells from animals tolerant to a fully allogeneic allograft to these subsets from naive animals. Paradoxically tolerant CD4+CD25+T cells did not proliferate to specific donor, but did to third party, whereas naive CD4+CD25+T cells proliferated to all alloantigens. Proliferation of tolerant and naive CD4+T cells to specific donor and self was similar, and removal of CD25+ cells enhanced proliferation except that of tolerant cells to specific donor. These studies paradoxically suggested tolerant CD4+CD25+ T cells were not inhibiting proliferation of CD4+CD25–T cells to specific donor.
It is known that tolerant CD4+CD25+T cells are short lived, and require cytokines other than IL-2 to survive. We showed that tolerant CD4+CD25+T cells response to specific donor but not to third party or self could be enhanced by adding either IFNγ or IL-5 to culture, but not by other cytokines including IL-4, IL-10, IL-13, and TGF-Β. Receptors for IL-5 and IFN-γ are expressed by tolerant but not naive CD4+CD25+T cells. Responses of tolerant CD4+T cells are inhibited by addition of either IFNγ or IL-5.
These findings were consistent with transplant tolerance being mediated by CD4+CD25+T cells that is short lived ex vivo. The tolerance mediating CD4+CD25+FOXP3+ T regulatory cells only survive is stimulated by specific donor alloantigen and either IFNγ or IL-5 produced by alloactivated Th1 and Th2 cells. One or more of these differences in reactivity of CD4+T cell subsets may provide a test for transplant tolerance.
CITATION INFORMATION: Hall B, Robinson C, Plain K, Verma N, Tran G, Carter N, Nomura M, Boyd R, Hodgkinson S. In Vitro Reactivity of CD4+ T Cells Subsets from Hosts with Antigen Specific Transplant Tolerance Mediated by CD4+CD25+T Cells. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Hall B, Robinson C, Plain K, Verma N, Tran G, Carter N, Nomura M, Boyd R, Hodgkinson S. In Vitro Reactivity of CD4+ T Cells Subsets from Hosts with Antigen Specific Transplant Tolerance Mediated by CD4+CD25+T Cells. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/in-vitro-reactivity-of-cd4-t-cells-subsets-from-hosts-with-antigen-specific-transplant-tolerance-mediated-by-cd4cd25t-cells/. Accessed September 21, 2017.
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