EFFECT OF DSG ON XENOGENEIC IMMUNE REACTIVITY WITH SPECIAL EMPHASIS ON HUMAN ANTI-PIG CELLULAR REACTIONS IN-VITRO

The effect of the immunosuppressive drug 15-deoxyspergualin (DSG) on x enogeneic human anti-porcine cellular reactivity in vitro, including M LR induced proliferation, interleukin-2 (Il-2) production, generation of cytotoxic cells, and the effect on antibody-dependent cellular cyto toxicity (ADCC), were compared with the effects of cyclosporin A (CsA) and/or FK506. The cytotoxic response was evaluated for both direct an d indirect pathways for antigen presentation. In addition, the effects of DSG and CsA on antibody production to pig peripheral blood lymphoc ytes (PBL) in mice was studied. The degree of immunosuppression of xen ogeneic and allogeneic cellular responses was compared. CsA and FK506 effectively inhibited proliferation and Il-2 production induced by all ogeneic human PBL or xenogeneic porcine PBL, whereas DSG did not have any effect on these responses. However, DSG suppressed both the alloge neic and xenogeneic in vitro induced cytotoxic responses, to the same level whether induced via the direct or indirect pathways of immune ac tivation. In contrast, CsA inhibited cytotoxicity induced by xenogenei c cells via the direct but not via the indirect pathway. No effect of FK506 and DSG on ADCC was demonstrated. A 5-day treatment with DSG or CsA of mice immunized with pig PBL partly suppressed antibody producti on. In DSG treated mice anti-pig PBL antibodies were produced, but tit ers were lower than in nontreated or CsA treated mice. The results ind icate that DSG may be more effective than CsA/FK506 in inhibiting cyto toxic responses and antibody production induced by xenogeneic pig cell s. A possible explanation could be that cytotoxicity induced via the i ndirect activation pathway of xenoreactivity is mediated to a high deg ree by CD3(-)CD16(+) (natural killer) NK-like cells, and that stimulat ion of these cells may be more sensitive to DSG than to CsA/FK506.