T CELL RESPONSES IN BONE MARROW TRANSPLANTATION

担心功能有效的T细胞库可能永远不会

Concerns that a functionally effective T cell repertoire might never develop in the setting of MHC-mismatched marrow transplantation are based on defective T cell responses in vivo observed in murine bone marrow chimeras constructed between MHC disparate strains. The incompetence is not due to inherent T cell defects, but rather to the restriction specificities of the T cells such that those MHC determinants recognized as self (host type) are not expressed by the antigen presenting cells which are of donor type. The T cell response to antigen is therefore defective. To evaluate whether T cell maturation is comparable in mouse and man, the development of T cell responses in a primate, the rhesus monkey, has been studied. The biology of T cell recovery has first been investigated in animals following T cell depleted autologous marrow transplantation. The time course of CD4+ T cell reconstitution and the time course of the development of in vivo T cell immunocompetence as defined by the ability to respond to an organ allograft correlated with the number of T cells infused in the marrow, and did not correlate with marrow cell dose or with time of hematopoietic reconstitution, raising the possibility that residual T cells in the infused T cell depleted marrow played a central role in the generation of subsequent T cell populations. This would imply that the generation of T cells in marrow grafted primates may not be the same as in the mouse.