HLA-restricted lysis of herpes simplex virus-infected monocytes and macrophages mediated by CD4+ and CD8+ T lymphocytes.
Freshly isolated human peripheral blood monocytes and in vitro monocyte-derived macrophages were infected with HSV type 1 and used as target cells in a cell-mediated cytotoxicity assay. PBMC from both HSV-immune and non-immune donors were stimulated in vitro for 5 days with UV-inactivated HSV Ag and used as effector cells. Effectors from HSV-immune donors mediated virus-specific lysis of both monocyte and macrophage targets, whereas effectors from non-immune donors failed to mediate target cell lysis. Mean virus-specific lysis of autologous monocytes was (8.5 +/- (+/- 2.0)%) compared to a threefold greater virus-specific lysis of autologous macrophages (24.7 (+/- 4.3)%). More than 70% of this lysis was mediated by CD16- T lymphocytes. Further analysis demonstrated that the majority of the lysis against autologous and allogeneic targets was HLA-DR-restricted and mediated by CD4+ CTL. However, CD8+ CTL also contributed to the lysis of autologous targets as well as allogeneic targets having a common HLA-A and/or -B determinant. The HLA-restricted cytotoxicity was virus-specific as HSV-infected, but not CMV-infected, cells were lysed. CTL-mediated lysis of HSV-infected monocytes and macrophages may be of significance in the anti-viral and immunoregulatory host response.
Torpey
D J
DJ
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Lindsley
M D
MD
Rinaldo
C R
CR
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006561:Herpes Simplex / Q000235:genetics / Q000276:immunology*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D000939:Epitopes; D006680:HLA Antigens