Intrathymic selection of murine TCRαβ+CD4−CD8− thymocytes

Abstract

The CD4⁻CD8⁻ thymocyte population contains the precursors of all other thymocytes. However, it also contains a significant proportion of cells which express surface TCRαβ, and have little or no precursor activity. Like peripheral T cells, but unlike most other thymocytes, these TCRαβ⁺CD4⁻CD8⁻ thymocytes do not express heat stable antigen. Both the origin and developmental status of these cells are unclear, and are the subject of this report. We have measured the proportion of V_β8.1⁺ cells amongst TCR⁺HSA⁻CD4⁻CD8⁻ thymocytes In Mls-1^a versus Mls-1^b mice, in order to determine whether they have undergone negative selection. The proportions were similar in both strains, in contrast to mature T cells, indicating that neither they nor their precursors had undergone clonal deletion. We also measured the accumulation of these cells over the early life of the animal and found that It was extremely slow. Our data also show that although TCR-V_β8.1⁺ cells are reactive to Mls-1^a in association with MHC class II, most mature TCR-V_β8.1⁺ cells in Mls-1^b mice are CD8 suggesting an additional reactivity with MHC class I. We raise the possibility that TCR-V_β8.1⁺CD4⁻CD8⁻ thymocytes are derived from TCR-V_β8.1⁺CD4⁺CD8⁺ thymocytes, and that the reactivity of TCR-V_β8.1 with both MHC classes I and II has resulted in the down-regulation of both CD4 and CD8.