Positive selection is not required for thymic maturation of transgenic gamma delta T cells.
Previously published reports describing thymic differentiation in two TCR gamma delta transgenic mouse models have suggested that gamma delta T cells require MHC-mediated positive selection to reach full maturity. Recent studies indicate that recognition of antigen by mature gamma delta T cells is not MHC restricted, raising the issue of why developing gamma delta T cells would even require MHC-driven positive selection. Therefore, we have reinvestigated the requirements for development and selection in G8 gamma delta T cell receptor (TCR) transgenic mice. Analyses of absolute cell numbers, phenotypic subsets, and functional competence of thymic and peripheral G8 gamma delta T cells indicate that these cells can fully mature in class I MHC-deficient mice. Moreover, mixed bone marrow chimeras demonstrate that gamma delta T cells of mutant B2-microglobulin (beta 2m zero) origin are partially deleted in the presence of H-2d-bearing thymocytes (previously believed to be the haplotype mediating positive selection). We conclude that there is no requirement for class I-like molecules for the maturation/development of these transgenic gamma delta T cells and that the differences in thymocyte phenotype and number observed are, instead, attributable to effects of clonal deletion.
Schweighoffer
E
E
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0420, USA.
Fowlkes
B J
BJ
D000818:Animals; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000276:immunology / Q000528:radiation effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology; D002678:Chimera; D003433:Crosses, Genetic; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000172:deficiency
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D001613:beta 2-Microglobulin