Human anti-pig cell-mediated cytotoxicity in vitro involves non-T as well as T cell components

Human anti-pig cell-mediated cytotoxicity was studied in vitro. Unprimed human peripheral blood lymphocytes (PBL) were able to lyse pig targets but not human targets when the assay was performed in human serum (HS), Much less, but still detectable, lysis was obtained using fetal calf serum (FCS). Human PBLs cultured for 6 days in FCS without stimulating cells showed substantial lysis of pig targets, This lysis was increased by the addition of human IL-2. Unseparated human PBLs stimulated for 6 days with pig cells in serum-free media lysed pig targets expressing the same or different SLA antigens as the stimulating cells. This lysis could not be significantly inhibited by anti-CD3 or anti-CD8 blocking antibodies during the effector phase of the assay. T cell-enriched human PBLs treated with anti-CD16 and anti-CD56 antibodies plus complement also lysed pig targets. These effector cells were significantly inhibited by anti-CD3 and anti-CD8 antibodies but not by anti-CD4 antibodies. Furthermore, these primed T cell effecters could only lyse pig targets that shared the same MHC class I antigens as the sensitizing stimulators. These results suggest that human anti-pig cell-mediated cytotoxicity in vitro has at least three different components in bulk culture: 1) an ADCC component depending on natural antibodies from human serum, 2) an NK and/or a LAK cell component that is enriched by in vitro culture and interleukin-2 (IL-2), and (3) an allospecific T cell component, involving CD3+, CD8+, class I-specific effector cells.