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Signal via IL‐12Rβ2 Negatively Controls Intrathymic Maturation
Author(s) -
Zhang GuangXian,
Yu Shuo,
Gran Bruno,
Rostami Abdolmohamad
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.843.4
Subject(s) - double negative , cd8 , t cell receptor , thymocyte , biology , receptor , stimulation , t cell , endocrinology , medicine , cd3 , immunology , microbiology and biotechnology , immune system
Mice lacking IL‐12 and its responsiveness exhibited more severe inflammatory responses and were more susceptible to autoimmune diseases than wild type mice, yet the mechanism underlying this phenomenon is not clear. An increased number of CD4 + T cells has been observed in the periphery of IL‐12Rβ2 −/− mice compared to wild type mice, indicating that IL‐12 responsiveness is involved in either decreased T cell death and/or increased T cell generation. We report here that thymocytes in mice deficient in IL‐12Rβ2, thus lacking IL‐12 responsiveness, undergo dramatically accelerated maturation. This mainly occurs at the stage from double positive (DP) to single positive (SP), resulting in higher numbers of CD4 and CD8 SP cells in these mice. No difference was observed in percentage and absolute number of apoptotic cells between the two mouse trains. Accelerated maturation also occurs at the stage from double negative (DN) to DP, given the significantly lower CD24 and higher TCRαβ and IL‐7Rα expression in these subsets of IL‐12Rβ2‐deficient mice. This occurs not only in mice injected with anti‐CD3 to mimic pre‐T cell receptor stimulation, but also in mice immunized with autoantigen to induce EAE. Thus, signals through IL‐12Rβ2 negatively regulate thymocyte maturation and play a crucial immunoregulatory role in controlling autoimmunity.