A CORTISONE SENSITIVE CD3LOW SUBSET OF CD4+CD8-THYMOCYTES REPRESENTS AN INTERMEDIATE STAGE IN INTRATHYMIC REPERTOIRE SELECTION

Two populations of CD4 single positive (SP) thymocytes were found in transgenic mice bearing class I-restricted MIs-1a reactive (V-beta-8.1) TCR genes in the absence of the restriction element. CD3high CD4 SP cells were deleted in the presence of MIs-1a and were cortisone resistant, whereas CD3low CD4 SP cells were not deleted in the presence of MIs-1a and were cortisone sensitive. Intravenous transfer of CD3low CD4 SP cells into nude mice resulted in significant peripheral expansion of these cells with apparent upregulation of CD3. These data indicate that CD3low CD4 SP thymocytes represent an intermediate stage in the transition from CD3low double positive (DP) to CD3 high SP thymocytes and raise the possibility that these cells may have undergone positive but not negative selection events (at least to MIs-1a). Furthermore the fact that CD3 high DP thymocytes were also deleted by MIs-1a in these mice suggests strongly that sensitivity to MIs-1a deletion is dependent upon stage of thymic maturation (as revealed by TCR density) rather than CD4/CD8 phenotype.