The majority of postselection CD4+ single-positive thymocytes requires the thymus to produce long-lived, functional T cells.
We have previously isolated, and characterized in vitro, two subsets of CD4hi T cell receptor (TCR)hi single positive (SP) thymocytes: CD8- and CD8lo. In this report, we have analyzed phenotypic, functional, and developmental characteristics of these "late" CD4hi SP thymocyte subsets. The TCRhi phenotype and the elimination of T cells expressing TCR V beta segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4hi thymocytes were functional, as judged by their ability to: (a) induce lethal graft versus host disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c) proliferate, rather than undergo apoptosis, in response to in vitro TCR cross-linking. By contrast, CD8lo4hi cells could not induce GVHD, were unable to expand (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR cross-linking. However, when reintroduced into the thymus, these cells matured into functional, long-lived CD8-4hi lymphocytes. These results document an obligatory requirement for the thymic microenvironment in the final maturation of the majority of CD4hi SP postselection thymocytes, and demonstrate the existence of a previously unrecognized control point in T cell development.
Dyall
R
R
Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021.
Nikolić-Zugić
J
J
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis; D002454:Cell Differentiation; D002465:Cell Movement; D002469:Cell Separation; D002470:Cell Survival; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D016131:Lymphocyte Subsets / Q000166:cytology*; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D013950:Thymus Gland / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D000099192:CD69 Antigens