The majority of CD4⁺8^- thymocytes are functionally immature

The thymus is the major site of T cell development and repertoire selection. During these processes, T cells segregate into two subsets that express either CD4 or CD8 accessory molecules, the phenotype of peripheral T cells. Analysis of CD4⁺8^- thymocytes revealed that the majority of these cells express the heat-stable Ag (HSA) but not the nonclassical class I Ag, Qa-2. This HSA⁺, Qa-2^- phenotype is similar to that of the less mature, CD4⁺8⁺ thymocytes. The remaining CD4⁺8^- thymocytes possess the HSA^-, Qa-2⁺ phenotype of peripheral T cells. To determine whether the Qa-2^-, CD4⁺8^- thymic subset is fully mature, we have analyzed the functional status of these CD4⁺8^- subpopulations. The results indicate that only those thymocytes which express Qa-2 are fully responsive to anti-TCR stimulation in a manner analogous to peripheral T cells. The Qa-2^- subset is nonresponsive to stimulation by anti-TCR antibodies that have been immobilized to plastic, even in the presence of lymphokines or syngeneic APC. This subset is, however, capable of proliferating to allogeneic cells or to anti-TCR on the surface of syngeneic APC, although not to the levels achieved by Qa-2⁺ thymocytes. Thus, the Qa-2^- subset appears to require additional interactions which are not necessary for peripheral T cells or Qa-2⁺ thymocytes. Relevant to this issue, the Qa-2⁺ thymocyte subset does not appear until relatively late in development, and does not reach adult frequencies until several weeks after birth. These results would suggest that there is a progression from HSA⁺, Qa-2^- to HSA^-, Qa-2⁺ which parallels the maturation of functional responsiveness. These findings are important to understanding T cell selection since thymocytes with such a decreased responsiveness may have a differential capacity for tolerance induction. The results presented suggest that the bulk of CD4⁺8^- thymocytes are not fully mature and that Qa-2 may serve as a marker for T cells with a more complete functional competence.