Extrathymic T-lymphocyte development.

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Chronic exposure to oncostatin M (OM) induces massive thymus-independent extrathymic T-cell development, which takes place solely in the lymph nodes (LN), probably because of the high density of OM receptor on LN postcapillary venules. In contrast to what is observed in other models of extrathymic T-cell development, the proportions of double-negative (DN), double-positive (DP), and single-positive (SP) T cells in the OM+ LN reproduce those found in a thymus, and the T-cell receptor (TCR) repertoire of the SP cells is diversified. Analyses of T-cell development in hematopoietic chimeras expressing MHC class I only on hematopoietic or non-hematopoietic cells showed that MHC class I on hematopoietic cells was sufficient for positive selection of a diversified repertoire of CD8 T cells. However, studies of TCR-transgenic mice revealed that the hierarchy of TCR clonotype selection is not the same as in the thymus. Even though there is no cortico-medullary segregation in the OM+ LN, negative selection of T cells bearing the 2C and the anti-H-Y TCR was very effective. The progeny of the thymic-independent differentiation pathway regulated by OM is polyclonal in terms of Vβ usage, exhibits an activated-memory phenotype, and displays a rapid turnover rate. Following TCR ligation, extrathymic T cells begin to proliferate earlier than thymus-derived T cells, but their expansion is limited by a high apoptosis rate. This model provides a unique opportunity to elucidate critical interactions between T cell progenitors and stromal cells, that is, the essence of a primary T lymphoid organ.“We shall come to regard the presence of lymphocytes in the thymus as an evolutionary accident of no very great significance [1].”—P.B. Medawar (Nobel Prize in Medicine, 1960)