Intrathymic maturation of CD4+ T-lymphocytes in an MHC class II deficient transplant model

Major histocompatibility complex (MHC) class II knockout (class II-) mice fail to generate CD4+ CD8- T-lymphocytes. We were interested in determining whether these class II- mice could be reconstituted with CD4+ CD8- T-lymphocytes following marrow transplantation from normal (class II+) donors. Transplantation of class II+ marrow into lethally irradiated class II- recipients failed to generate peripheral CD4+ CD8- T-lymphocytes. Unexpectedly, however, transplantation of class II marrow into class II+ recipients also resulted in a deficiency of CD4+ CD8- cells. Analysis of intrathymic T cells showed normal distribution of CD4 and CD8 single and double positive or negative thymocytes in normal recipients, while class II- recipients always lacked CD4+ CD8- T cells intrathymically. These results suggest, therefore, that T-cell maturation in mice requires the presence of MHC class II antigens not only in the thymus but also on immature, marrow-derived pre-thymocytes.