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Thymus machinery for T-cell selection.

ABSTRACT: An immunocompetent and self-tolerant pool of naive T cells is formed in the thymus through the process of repertoire selection. T cells that are potentially capable of responding to foreign antigens are positively selected in the thymic cortex and are further selected in the thymic medulla to help prevent self-reactivity. The affinity between T-cell antigen receptors expressed by newly generated T cells and self-peptide-major histocompatibility complexes displayed in the thymic microenvironments plays a key role in determining the fate of developing T cells during thymic selection. Recent advances in our knowledge of the biology of thymic epithelial cells have revealed unique machinery that contributes to positive and negative selection in the thymus. In this article, we summarize recent findings on thymic T-cell selection, focusing on the machinery unique to thymic epithelial cells.

SUBMITTER: Kondo K

PROVIDER: S-EPMC6400048 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Thymus machinery for T-cell selection.

Kondo Kenta K Ohigashi Izumi I Takahama Yousuke Y

International immunology 20190301 3

An immunocompetent and self-tolerant pool of naive T cells is formed in the thymus through the process of repertoire selection. T cells that are potentially capable of responding to foreign antigens are positively selected in the thymic cortex and are further selected in the thymic medulla to help prevent self-reactivity. The affinity between T-cell antigen receptors expressed by newly generated T cells and self-peptide-major histocompatibility complexes displayed in the thymic microenvironments ...[more]

PMID: 30476234

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Project description:To elucidate the funciton of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tl alpha 2-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tla2-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg. Tla2-3-1, Tg. Tla2-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg. Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tla2-3-1 and Tg.Tla2-3-2, respectively, expressed TCR gamma delta, whereas almost all those from C3H expressed TCR alpha beta. The MLC from Tg. Tla2-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg. Tla2-3-1 had little or none. The generation of gamma delta CTL recognizing TL in Tg. Tla2-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 gamma delta CTL clones were established from Tg. Tla2-3-2, whereas none were obtained from C3H. Of the 14 gamma delta CTL clones, 8 were CD8+ and 6 were CD4-CD8- double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCR gamma delta and CD3, and also by antibodies to CD 8 alpha and CD8 beta in CD8+ clones, showing that the activity was mediated by TCR gamma delta and coreceptors. The thymic origin of these gamma delta CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8 alpha beta heterodimers in CD8+ clones on their surfaces and by the usage of TCR V gamma 4 chains in 12 of the 14 clones. Taken together, these results suggest that Tla2-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of gamma delta T cells.

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Thymus machinery for T-cell selection.

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Thymus machinery for T-cell selection.

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