Ultraviolet B-modified donor-specific blood transfusions and peritransplant cyclosporine in the induction of specific unresponsiveness to organ allografts

Numerous reports support the original observation by Salvatierra et al that pretreatment with donor-specific blood transfusions (DST) improves renal allograft survival in one-haplotype-matched donor-recipient pairs with high mixed lymphocyte reactivity (MLR). The risk of recipient sensitization from DST continues to be a significant obstacle to the general acceptance of this concept. The use of concomitant administration of immunosuppressants with DST has reduced the incidence of donor-specific sensitization; but methods for further reduction or elimination of sensitization with DST, without losing their beneficial immunologic influence, continue to be sought. This review summarizes our experience with a new approach to this problem using ultraviolet B (UV-B) irradiation, which modulates the sensitization effect of DST. It has been demonstrated that UV-B irradiation of DST (UV-DST) inactivates the Ia positive, antigen-presenting cells (APC) in blood and abrogates their capacity to stimulate blastogenesis of responder cells in an MLR. This observation agrees with the hypothesis of Bach et al that the loss of the stimulating effect of UV-irradiated lymphocytes in MLR is due to their inability to activate the helper T cell population. On the other hand, the two-signal approach for T cell activation during immune response proposed by Lafferty and Woulnough, which requires antigen binding to the T cell receptor and an inductive stimulus that is delivered only by metabolically active cells or by products of metabolically active cells, supports our observations. Ultraviolet irradiation inactivates the APC and impairs the inductive stimulus without affecting antigen recognition. We, therefore, hypothesized that the impairment of APC in DST by UV-B irradiation would permit misrepresentation of non-self as self, probably by the host's own APC, which would lead to donor-specific immunologic unresponsiveness to subsequent organ allografts.