Small cortical thymocytes are subject to positive selection

Abstract

To determine the developmental stages at which positive selection can act to produce mature T cells, CD4+8+3(lo) thymocytes of large dividing type and of small nondividing type were sorted and transferred into the thymus of nonirradiated Thy-1 congenic recipient mice. In contrast to earlier studies, the small as well as the large thymocytes produced mature CD4+8-3(hi) and CD4-8+3(hi) progeny, although production was less efficient from the small cells. The relative efficiency of small cells was increased and was close to that of large cells when bcl-2/anti-HY T cell receptor (TCR) αβ transgenic donors were used to improve cell survival, overcome stress effects of the transfer process, and increase the frequency of selectable cells. The results from transferring small CD4+8+3(lo) thymocytes expressing a TCR transgene from a nonselecting to a selecting thymic MHC environment also confirmed that the small cells were capable of being selected and maturing. Thus the developmental window available for positive selection includes the small CD4+8+3(lo) thymocytes. The results also showed a striking difference in the kinetics of production of mature progeny from the transferred CD4+8+3(lo) precursors. CD4+8-3(hi) cells appeared several days before CD4-8+3(hi) cells, apparently because the CD4-8+ lineage cells spent several days in transit as CD4+8+3(hi) intermediates before losing CD4. Most CD4+8- lineage cells on the other hand, either passed very rapidly through this intermediate stage, or lost CD8 before increasing the expression of CD3.