T-CELL differentiation in the thymus is thought to involve a progression from the CD4−CD8− phenotype through CD4+CD8+ intermediates to mature CD4+ or CD8+ cells1-3. There is evidence that during this process T cells bearing receptors potentially reactive to 'self are deleted by a process termed 'negative selection'4-10. One example of this process occurs in mice carrying polymorphic Mis antigens, against which a detectable proportion of T cells are autoreactive. These mice show clonal deletion of thymic and peripheral T-cell subsets that express the autoreactive Vβ3 segment of the T-cell antigen receptor, but at most a two-fold depletion of thymic cells at the CD4+CD8+ stage5-7. By contrast, transgenic mice bearing both α and β chain genes encoding autoreactive receptors recognizing other ligands, show severe depletion of CD4+CD8+ thymocytes as well8,9, suggesting that negative selection occurs much earlier. We report here the Mis 2a/3a mediated elimination of T cells expressing a transgene encoded Vβ3-segment, in T-cell receptor α/β and β-transgenic mice. Severe depletion of CD4+CD8+ thymocytes is seen only in the α/β chain transgenic mice, whereas both strains delete mature Vβ3 bearing CD4+ and CD8+ T cells efficiently. We conclude that severe CD4+CD8 thymocyte deletion in α/β transgenic mice results from the premature expression of both receptor chains, and does not reflect a difference in the timing or mechanism of negative selection for Mis antigens5-7 as against the allo- and MHC class 1-restricted antigens used in the other studies8-9.
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