Mechanisms by which T cell populations are generated are relevant to considerations of immunoreconstitution in situations in which T cell depletion occurs. Studies in rhesus monkeys investigating T cell generation following T cell depleted autologous marrow transplantation provided evidence that residual T cells in infused T cell-depleted marrow play a central role in the generation of subsequent T cell populations. This possibility was confirmed in murine studies in which three T cell progenitor pools were identified which contribute to final T cell repopulation following marrow transplantation. It was found that cells arising from a peripheral, mature lymphocyte precursor pool were of memory phenotype, and that only T cells generated by a thymic pathway contained large numbers of naive T cells. This information has been applied to studies of T cell generation in patients receiving chemotherapy which have shown an age dependence on generation of T cells by the thymus & have provided a paradigm by which T cell generation might be studied in other circumstances. The functional capacities of regenerated T cell populations is also of interest. The human T helper cell response to xenogeneic MHC encoded antigens expressed by stimulating murine cell populations has been studied & 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 & presentation in association with human Class II gene products. The requirement for reprocessing of murine antigen & presentation by responder-type cells (rather than murine stimulating cells) was found to be due to lack of both murine antigen presenting cell activation & responder human T cell activation. Further, GM-CSF provided a sufficient signal to murine APC to result in upregulation of B7-2, enabling murine antigen presenting cells to directly present antigen to human T helper cells.
