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Extrathymic positive selection of αβ T-cell precursors in nude mice

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Abstract

T LYMPHOCYTES expressing αβ T-cell receptors with sufficient affinity to major histocompatibility complex (MHC) molecules expressed on thymus epithelial cells are positively selected and mature to functional T cells1–6. But several studies have demonstrated that athymic nude mice7–9grafted with MHC-incompatible thymuses developed T cells specific for nude host rather than thymic MHC10–14. We examined this paradox by analysing the specificity of T lymphocytes derived from nude mice. We report here that nude T lymphocyte precursors transferred to allogeneic SCID (severe combined immunodeficiency) mice with a functioning thymus (but lacking T or B cells15–17) generated host MHC-restricted effector T cells but also contained T cells restricted to donor MHC. If nude T cells were depleted from nude lympho-haemopoietic donor cells before or after transfer, only host MHC-specific T cells matured. The results may explain the unusual MHC specificities of nude T lymphocytes described in earlier studies 10–14and demonstrate two separate differentiation steps: in nude mice, T cells may be positively selected for self-MHC restriction specificity extrathymically; then a functional thymus is required for efficient T cell maturation.

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Authors and Affiliations

  1. Laboratory for Experimental Pathology, Institute of Pathology, University Hospital, CH-8091, Zurich, Switzerland

    Daniel E. Speiser, Ursula Stiibi & Rolf M. Zinkernagel

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  1. Daniel E. Speiser
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  2. Ursula Stiibi
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  3. Rolf M. Zinkernagel
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Speiser, D., Stiibi, U. & Zinkernagel, R. Extrathymic positive selection of αβ T-cell precursors in nude mice. Nature 355, 170–172 (1992). https://doi.org/10.1038/355170a0

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