Faculty Research 1990 - 1999

Positive selection of T-lymphocytes induced by intrathymic injection of a thymic epithelial cell line.

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Antigens-Viral: im, Base-Sequence, Cytotoxicity-Immunologic, H-2-Antigens: im, Immunity-Cellular, Mice, Mice-Transgenic, Molecular-Sequence-Data, Oligodeoxyribonucleotides, Orthomyxoviridae: im, Radiation-Chimera, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes-Cytotoxic: im, Thymus-Gland: cy, Tumor-Cells-Cultured, Vesicular-Stomatitis-Virus: im

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Nature 1992 Oct 22;359(6397):729-32


T lymphocytes recognize antigens as peptide fragments associated with molecules encoded by the major histocompatibility complex (MHC) and expressed on the surface of antigen-presenting cells. In the thymus, T cells bearing alpha beta receptors that react with the MHC molecules expressed by radioresistant stromal elements are positively selected for maturation. In (A x B-->A) bone marrow chimaeras, T cells restricted to the MHC-A haplotype are positively selected, whereas MHC-B-reactive thymocytes are not. We investigated whether the introduction of particular thymic stromal elements bearing MHC-B molecules could alter the fate of B-reactive T cells in these (A x B-->A) chimaeras. Thymic epithelial cell (TEC) lines expressing H-2b were introduced by intrathymic injection into (H-2b/s-->H2s) bone marrow chimaeras and we measured their ability to generate H-2b-restricted cytotoxic T-lymphocytes (CTLs). We report here that one TEC line, 427.1, was able positively to select CTLs specific for influenza and vesicular stomatitis virus antigens in association with class I H-2b molecules. In addition, line 427.1 can process cytoplasmic proteins for presentation to H-2Kb- and H-2Db-restricted CTLs. Thus, a TEC line capable of normal class I MHC antigen processing and presentation in vitro can induce positive selection after intrathymic injection.

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