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Deletion Of Self-reactive Thymocytes Occurs At A CD4+8+ Precursor Stage

B. J. Fowlkes, R. Schwartz, D. Pardoll
Published 1988 · Biology, Medicine

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As T cells develop in the thymus, they become tolerant of self-antigens. A major advance in the understanding of how this process occurs was the direct demonstration that cells bearing autoreactive T-cell receptors (TCRs) are physically eliminated from the population of functionally mature T cells present in both the thymus and periphery1–3. We have sought to determine the developmental stage at which autoreactive T cells are eliminated by examining the expression of Vβl7a anti-I-E TCRs under various experimental conditions. In vivo antibody blockage of the CD4 molecule on developing thymocytes of I–E+ C57BR mice was found to inhibit the deletion of Vβ17a-bearing cells from the CD4–8+ single positive thymocyte subset. This result provides strong evidence that deletion of potentially autoreactive T cells occurs at a CD4+8+ precursor stage, that the non-clonally distributed accessory molecules (CD4, CD8) are significant participants in the self-recognition process that leads to clonal elimination, and that thymic class II major histocompatibility complex (MHC) molecules can influence the repertoire of CD4–8+ cells.
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