A NOVEL IN VIVO HUMAN CYTOTOXIC T CELL

Non-MHC restricted cytotoxic lymphocytes appear in vivo during acute EBV induced infectious mononucleosis (IM). Complement depletion with T-cell (OKT3) and NK-cell (Leullb and NKH-la) monoclonal antibodies demonstrated this non-MHC restricted activity to be mediated primarily by cytotoxic T-lymphocytes (CTL). Depletion of NK-cells, with a 76% (Leullb) and 54% (NKH-la) reduction in the lysis of K562, resulted in a slight (<30% for Leullb and NKH-la) reduction in the nonrestricted lysis of two allogeneic EBV infected lymphoblastoid cell lines (LCL). Depletion of T-cells by OKT3 and complement abolished (96% reduction) the nonspecific lysis of these two LCL. Complement depletion with antibodies to CDS (OKT8) and HLA-DR decreased the nonspecific response by 89% and 62%, respectively. Monoclonal antibody inhibition studies with antibodies to CD3 (OKT3), CDS (OKT8) demonstrated this nonspecific response to be mediated through the CD3/T-cell receptor and to use the CDS antigen as an accessory molecule; OKT3 and OKT8 monoclonal antibodies inhibited the nonspecific lysis of three LCL by an average of 79% and 74%, respectively. The specificity of this inhibition was demonstrated by the lack (7<10%) of inhibition by the anti-CD5 pan T-cell monoclonal antibody OKT1. These results clearly demonstrate that IM non-MHC restricted CTLs are of T-cell origin. The lack of NKH-la expression and sensitivity of cytolytic activity to anti-CD8 antibodies distinguishes acute IM CTLs from previously described non-MHC restricted human cytotoxic lymphocytes. (Lanier et al, Immuno. Today vol 7).