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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009288-03
Application #
3813478
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code