Class II-Positive Hematopoietic Cells Cannot Mediate Positive Selection of CD4+T Lymphocytes in Class II-Deficient Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-04, Vol.90 (7), p.2779-2783
• Main Authors: Markowitz, Jay S., Auchincloss, Hugh, Grusby, Michael J., Glimcher, Laurie H.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone marrow; Bone Marrow - radiation effects; Bone Marrow Cells; Bone Marrow Transplantation - immunology; Bones; CD4 Antigens - immunology; Cellular biology; Chimera; Chimeras; Crosses, Genetic; Epithelium; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hematopoietic Stem Cells - immunology; Histocompatibility Antigens Class II - immunology; Immunity (Disease); Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Nude; Molecules; Positive selection; Rodents; T cell antigen receptors; T lymphocytes; T-Lymphocyte Subsets - immunology; Thymocytes; Thymus Gland - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.7.2779

Generation of immunocompetent α/β 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.