Concerns that a functionally effective T cell repertoire might never develop in the setting of MHC-micmatched marrow transplantation are based on the 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 immuno-competence 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 susequent 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
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009288-02
Application #
3916429
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code