IL-7 DRIVES DONOR T-CELL PROLIFERATION AND CAN COSTIMULATE CYTOKINE SECRETION AFTER MHC-MATCHED ALLOGENEIC BONE-MARROW TRANSPLANTATION

Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T c ells into BALB/c recipients ultimately results in chronic graft-vs-hos t disease (GVHD) and mortality 8 to 12 wk post-transplant. We have ide ntified IL-7-specific mRNA in the spleens of BALB/c bone marrow transp lantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-trans plant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2 -dependent and -independent components were identified. Depletion of r esponding cells before culture with anti-Thy-1.2 Ab virtually eliminat ed this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells pro liferate after exposure to this cytokine in vitro. To determine whethe r IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated wit h anti-T cell receptor (i.e., anti-VP) Ab was examined. IL-7 was demon strated to enhance IFN-gamma production by donor T cells postallogenei c BMT. These results suggest that a cytokine presumably produced in th e host for the physiologic function of hematologic reconstitution is p laying an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells.