RESTORATION OF ALLOGRAFT RESPONSIVENESS IN B RATS

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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 histoincompatible heterotopic cardiac allografts. The role of immune competent cells and lymphokine in restoring acute allograft rejection in these animals was investigated, noting that adoptive transfer of 108 sensitized splenocytes (sSL) plus interleukin 2-rich conditioned medium, IL-2 (CM) will reproducibly produce acute responsiveness toward longstanding, well-functioning, heart grafts. 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. The major cellular components within the spleen were separated using antibody techniques, and their individual role in the rejection reaction was assessed. Although 108 sSL plus IL-2 (CM) can produce acute rejection in a time comparable to that occurring in unmodified recipients (n = 20, MST [median survival time] .+-. SD = 8.4 .+-. 1.3 days), neither the T cell fraction (6 .times. 107) of 108 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) and could restore acute responsiveness. Increasing the numbers of T cells to 108 and transferring concomitantly with IL-2 (CM) again produced acute rejection (n = 4, MST .+-. SD = 9 .+-. 1.1 days). T cells apparently form the essential element of transfer in the B rat, although other cells present in SL appear necessary to provide an optimal milieu. This response may be independent of the route of administration or of higher doses of IL-2. 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.

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