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From the * Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland; the Interactions between major histocompatibility complex (MHC) molecules expressed on stromal cells and antigen-specific receptors on T cells shape the repertoire of mature T lymphocytes emerging from the thymus. Some thymocytes with appropriate receptors are stimulated
to undergo differentiation to the fully mature state (positive selection), whereas others with
strongly autoreactive receptors are triggered to undergo programmed cell death before completing this differentiation process (negative selection). The quantitative impact of negative selection on the potentially available repertoire is currently unknown. To address this issue, we
have constructed radiation bone marrow chimeras in which MHC molecules are present on radioresistant thymic epithelial cells (to allow positive selection) but absent from radiosensitive
hematopoietic elements responsible for negative selection. In such chimeras, the number of
mature thymocytes was increased by twofold as compared with appropriate control chimeras.
This increase in steady-state numbers of mature thymocytes was not related to proliferation, increased retention, or recirculation and was accompanied by a similar two- to threefold increase
in the de novo rate of generation of mature cells. Taken together, our data indicate that half to two-thirds of the thymocytes able to undergo positive selection die before full maturation due
to negative selection.
Lymphocyte Biology Section, Laboratory of Immunology, National
Institutes of Health, Bethesda, Maryland 20892-1892; and § Laboratory of Cellular and Molecular
Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, Maryland 20892-1892
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