Class II-positive hematopoietic cells cannot mediate positive selection of CD4+ T lymphocytes in class II-deficient mice.
Generation of immunocompetent alpha/beta T-cell receptor-positive T cells from CD4+CD8+ thymocytes depends upon their interaction with thymic major histocompatibility complex (MHC) molecules. This process of positive selection provides mature T cells that can recognize antigens in the context of self-MHC proteins. Previous studies investigating haplotype restriction in thymic and bone-marrow chimeras concluded that radioresistant thymic cortical epithelium directs the positive selection of thymocytes. There is controversy, however, as to whether intra- or extrathymic radiosensitive bone marrow-derived macrophage and dendritic cells also can mediate positive selection. To determine whether CD4+ T cells can be positively selected by hematopoietic cells, we generated chimeric animals expressing MHC class II molecules on either bone marrow-derived or thymic stromal cells by using a recently produced strain of MHC class II-deficient mice. CD4+ T cells developed only when class II MHC molecules were expressed on radioresistant thymic cells. In contrast to what recently has been observed for the selection of CD8+ T lymphocytes, MHC class II-positive bone marrow-derived cells were unable to mediate the selection of CD4+ T cells when the thymic epithelium lacked MHC class II expression. These data suggest that CD4+ and CD8+ T cells may be generated by overlapping, but not identical, mechanisms.
Markowitz
J S
JS
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Auchincloss
H
H
Grusby
M J
MJ
Glimcher
L H
LH
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002678:Chimera; D003433:Crosses, Genetic; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II