The elimination of T cells from marrow is of interest both in allogeneic and autologous marrow transplantation - - as a means of preventing graft versus host disease in allogeneic marrow transplantation and as a means of eliminating or purging malignant cells expressing T cell surface markers from marrow in treating T cell neoplasms by autologous marrow transplantation. We developed approaches for depleting normal and malignant T cell marrow populations from marrow; these approaches were then used in clinical protocols assessing the feasibility of utilizing allogenic HLA-mismatched, T cell depleted marrow and autologous marrow purged of malignant T cells in the treatment of aggressive hematolymphopoietic malignancies. Preclinical studies in rhesus monkeys demonstrated that CD4+ T cell reconstitution and development of in vivo T cell immunocompetence correlated with the number of T cells infused in the marrow 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 conclusion has been confirmed in murine studies in which three T cell progenitor pools have been identified which contribute to final T cell repopulation following marrow transplantation. The functional capacities of these regenerated T cell populations is also of interest. The human T helper cell response to xenogenic MHC encoded antigens expressed by stimulating murine cell populations has been studied and found to be of special use in the assessment of human T helper cell function in that this primary response requires reprocessing of the stimulating murine antigens and presention in association with human Class II gene products. The requirement for reprocessing of murine antigen and presentation by responder-type cells (rather than murine stimulating cells) was found to be due to a lack both of murine antigen presenting cell activation and responder T cell activation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Division of Cancer Biology and Diagnosis
United States
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