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Class II-Positive Hematopoietic Cells Cannot Mediate Positive Selection of CD4+ T Lymphocytes in Class II-Deficient Mice
Jay S. Markowitz, Hugh Auchincloss, Jr., Michael J. Grusby and Laurie H. Glimcher
Proceedings of the National Academy of Sciences of the United States of America
Vol. 90, No. 7 (Apr. 1, 1993), pp. 2779-2783
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2361621
Page Count: 5
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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.
Proceedings of the National Academy of Sciences of the United States of America © 1993 National Academy of Sciences