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. Unprim ed human peripheral blood lymphocytes (PBL) were able to lyse pig targ ets 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 stimul ating cells showed substantial lysis of pig targets, This lysis was in creased by the addition of human IL-2. Unseparated human PBLs stimulat ed for 6 days with pig cells in serum-free media lysed pig targets exp ressing the same or different SLA antigens as the stimulating cells. T his lysis could not be significantly inhibited by anti-CD3 or anti-CD8 blocking antibodies during the effector phase of the assay. T cell-en riched human PBLs treated with anti-CD16 and anti-CD56 antibodies plus complement also lysed pig targets. These effector cells were signific antly inhibited by anti-CD3 and anti-CD8 antibodies but not by anti-CD 4 antibodies. Furthermore, these primed T cell effecters could only ly se pig targets that shared the same MHC class I antigens as the sensit izing stimulators. These results suggest that human anti-pig cell-medi ated cytotoxicity in vitro has at least three different components in bulk culture: 1) an ADCC component depending on natural antibodies fro m human serum, 2) an NK and/or a LAK cell component that is enriched b y in vitro culture and interleukin-2 (IL-2), and (3) an allospecific T cell component, involving CD3+, CD8+, class I-specific effector cells .