The final maturation of at least some single-positive CD4(hi) thymocytes does not require T cell receptor-major histocompatibility complex contact

The majority (similar to 70%) of postselection CD4+ single-positive (SP) th ymocytes are CD8(lo)CD4(hi). These cells express very low levels of CD8, un detectable by now cytofluorimetric (FCM) analysis, but sufficiently high to allow purification by panning. Unlike the fully mature CD8-CD4(hi) thymocy te, which account for the remaining similar to 30% of the SP CD4(+) thymocy tes, CD8(lo)CD4(hi) cells are functionally immature and short-lived unless they receive an unidentified maturation signal from the thymus. In this stu dy, we tested the hypothesis that this signal is provided by a T cell recep tor (TCR)-major histocompatibility complex (MHC) class II interaction. Usin g intrathymic transfer, we show that the immature CD8(lo)CD4(hi) cells coul d complete their intrathymic maturation and populate the peripheral lymphoi d organs in the absence of MHC class II land class I) molecules. Furthermor e, in mice devoid of class II land class I) molecules, the progeny of CD8(l o)CD4(hi) cells was long-lived and functionally reactive to allogeneic clas s II molecules, although their numbers in the spleen and the mesenteric lym ph node were similar to 40-50% lower than those in class II+ mice 5 mo afte r transfer. Control experiments demonstrated that the surviving cells did n ot originate from the contaminating mature thymocytes. These results demons trate that the final maturation, proliferation, and peripheral survival (up to 5 mo) of at least some postselection CD4(+) SP cells do not require the TCR-MHC class II interaction. They also indicate that the TCR-MHC class II interaction(s) required for the intrathymic development of long-lived CD4( +) SP cells occurs before the CD4(hi) SP stage of development.