Deletion of self-reactive thymocytes occurs at a CD4⁺8⁺ precursor stage

Abstract

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 periphery^1–3. 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.