Cytotoxic T cells from a human chimera induce regression of Epstein-Barr virus-infected allogeneic host cells

The anti-Epstein—Barr virus (EBV) T cell response was studied in a severe combined immunodeficiency patient (PS) in whom stable peripheral blood chimerlsm was induced by transplantation of fetal liver stem cells from two donors. PS is characterized by a complete mismatch between the T lymphocytes, derived from the transplants, and all the other cells, including EBV+ B lymphocytes, of host origin. The patient's peripheral blood mononuclear cells were incubated with EBV and cultured for 1 month. In these cultures, T lymphocytes strongly inhibited the prollferation of the host EBV-infected lymphoblastoid cell line (PS-LCL) and, after expansion under repeated stimulation with PS-LCL in the presence of IL-2, they specifically inhibited the growth of host – HLA-matched LCL. In contrast, these T lymphocytes failed to recognize and to lyse EBV-infected HLA-identical targets. Lysis of PS-LCL was reduced after incubation with W6/32 or with anti-DR antibodies, suggesting a role for host HLA class I and HLA class II determinants in the lysis of the target cells. PS-HLA class I and HLA class II matched LCL were also killed. However, lymphocytes from the father or from the mother were not killed when not EBV-infected, indicating that host HLA antigens served as restricting determinants for the anti-viral T cells.