title: Defective in vitro production of influenza virus-specific cytotoxic T lymphocytes in ataxia-telangiectasia.
abstract: Peripheral blood mononuclear cells (PBMC) from patients with ataxia-telangiectasia (A-T) were studied for their capacity to proliferate and to generate influenza virus-specific cytotoxic T lymphocytes (CTL) after in vitro stimulation with influenza A/Hong Kong (A/HK (H3N2)) virus. PBMC from 11 patients proliferated poorly to A/HK and 10 of the 11 patients failed to exhibit significant CTL effector activity when tested on influenza A/HK virus-infected autologous target cells. In contrast, PBMC from each of 18 simultaneously studied, unrelated normal individuals proliferated to A/HK and generated influenza-immune CTL. In each of the 10 A-T patients, deficient CTL activity was shown to be due to a lack of generation of CTL and not to target cell resistance to lysis, because the virtually infected target cells of the patients were lysed by parental influenza-immune CTL. Determinations of T cell numbers and existing serum antibody titers to H3N2 influenza virus suggest this nonresponsiveness cannot be simply explained by a lack of T cells or the absence of exposure to type A (H3N2) influenza virus. Studies in which CTL were generated in A-T plasmas and during co-culture of PBMC from an A-T patient and an MHC-matched sibling failed to demonstrate either plasma or cellular suppression as a mechanism for the lack of CTL production in A-T patients. This immune defect in the production of cytotoxic effector T cells may be a cause of the increased frequency of infections and neoplasms observed in A-T patients.
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D001260:Ataxia Telangiectasia / Q000150:complications / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D017098:IgA Deficiency; D007108:Immune Tolerance; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D006680:HLA Antigens