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 chimerism 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 proliferation 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.
Plotnicky
H
H
Unité INSERM U80, Hôpital Edouard Herriot, Lyon, France.
Touraine
J L
JL
D000293:Adolescent; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006680:HLA Antigens; D006412:Hematopoietic Stem Cells / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D016511:Severe Combined Immunodeficiency / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D018183:Transplantation Chimera / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens