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.
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892.
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F
Ramsdell
M
M
Jenkins
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Dinh
B J
BJ
Fowlkes
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D003208:Concanavalin A / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007519:Isoantigens / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D008222:Lymphokines; C032907:Q surface antigens; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A