Restoration of allograft responsiveness in B rats. II. Requirements for lymphoid populations and lymphokine.

Abstract

B rats, produced by lethal x-irradiation of thymectomized animals that are then reconstituted with bone marrow cells from syngeneic, thymectomized, and thoracic-duct-drained donors, are unable to reject histoin-compatible heterotopic cardiac allografts. In these studies, we have continued to investigate the role of immune competent cells and lymphokine in restoring acute allograft rejection in these animals, noting that adoptive transfer of 10(8) sensitized splenocytes (sSL) plus Interleukin-2-rich conditioned medium, IL-2 (CM) will reproducibly produce acute responsiveness toward long-standing, well-functioning, heart grafts. We have now noted that sensitized lymph node cells or thoracic duct lymphocytes can also reverse the unresponsive state, with IL-2 rich conditioned supernatants increasing the effectiveness of small numbers of cells from these populations in inducing allograft rejection. Furthermore, the major cellular components within the spleen have been separated using antibody techniques, and their individual role in the rejection reaction has been assessed. Although 10(8) sSL plus IL-2 (CM) can produce acute rejection in a time comparable to that occurring in unmodified recipients (n = 20, MST +/- SD = 8.4 +/- 1.3 days), neither the T cell fraction (6 x 10(7] of 10(8) SL + IL-2 (CM) (n = 10, MST +/- SD = 17.4 +/- 7.3 days), nor addition of the adherent cell fraction to the T cell component (MST +/- SD = 18 +/- 2 days) or addition of the B cell fraction (MST +/- SD = 15.5 +/- 2.1 days) could restore acute responsiveness. However, increasing the numbers of T cells to 10(8) and transferring concomitantly with IL-2 (CM) again produced acute rejection (n = 4, MST +/- SD = 9 +/- 1.1 days). These data suggest that T cells form the essential element of transfer in the B rat, although other cells present in SL appear necessary to provide an optimal milieu. Our experiments also suggest that this response is independent of the route of administration or of higher doses of IL-2. Finally, using a dual allograft model, it appears that graft destruction is determined by the specific sensitivity of transferred SL; IL-2 (CM) being a nonspecific factor in the response.