INTRATHYMIC MATURATION OF CD4(-LYMPHOCYTES IN AN MHC CLASS-II DEFICIENT TRANSPLANT MODEL() T)

Major histocompatibility complex (MHC) class II knockout (class II-) m ice fail to generate CD4(+) CD8(-) T-lymphocytes. We were interested i n determining whether these class II- mice could be reconstituted with CD4(+) CD8(-) T-lymphocytes following marrow transplantation from nor mal (class II+) donors. Transplantation of class II+ marrow into letha lly irradiated class II- recipients failed to generate peripheral CD4( +) CD8(-) T-lymphocytes. Unexpectedly, however, transplantation of cla ss 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 thy mocytes in normal recipients, while class II- recipients always lacked CD4(+) CD8(-) T cells intrathymically. These results suggest, therefo re, that T-cell maturation in mice requires the presence of MHC class II antigens not only in the thymus but also on immature, marrow-derive d pre-thymocytes.