title: Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain: defective Fas ligand expression in gamma-chain-deficient mice.
abstract: Mice lacking the common cytokine receptor gamma-chain (gamma c) exhibit severely compromised lymphoid development. T cells that develop in these mice exhibit decreased Bcl-2 levels and accelerated apoptosis; nevertheless, these mice exhibit an age-dependent accumulation of activated CD4+ T cells. To investigate the basis for this accumulation, we analyzed both thymic and peripheral deletion in these mice. Gamma c-deficient mice had increased numbers of V beta 11+ T cells, consistent with a possible defect in Mtv-9-induced deletion; however, the deletion of V beta 5+ T cells by Mtv-9 and that of V beta 6+ T cells by Mls-1a were normal. Moreover, antigenic peptide could induce wild-type levels of deletion of CD4+ CD8+ thymocytes in TCR-transgenic gamma c-deficient mice. In contrast to this relatively normal deletion of thymocytes, bacterial superantigen (staphylococcal enterotoxin B)-induced elimination of peripheral T cells was greatly impaired, suggesting that defective peripheral deletion contributed to the accumulation of activated T cells. Interestingly, despite CD4+ T cell accumulation, these cells exhibited increased sensitivity to Fas-mediated death in vitro. Correction of the defect in Bcl-2 expression by mating to Bcl-2 transgenic mice augmented the splenic T cell accumulation and substantially enhanced the survival of gamma c-deficient T cells; however, these cells still exhibited significant Fas-mediated death, indicating that the increased Fas-mediated death was not simply due to diminished Bcl-2 expression. Moreover, these T cells exhibit decreased expression of Fas ligand, suggesting that Fas-bearing cells cannot be effectively eliminated in vivo in gamma c-deficient mice. Thus, gamma c-dependent signals play a role in peripheral T cell deletion, presumably by inducing Fas ligand on activated T cells.
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017637:Clonal Deletion / Q000235:genetics*; D053222:Fas Ligand Protein; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018121:Receptors, Cytokine / Q000172:deficiency* / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018121:Receptors, Cytokine