EBV-specific cytotoxic T cells can be generated in vitro in a secondary response. Several previous studies with bulk cultures provided evidence that cytotoxicity was restricted by HLA-A,B-related antigens. In the present family study, the EBV-specific cytotoxic T-cell response of a normal EBV-seropositive donor was analysed in detail by T-cell colony formation. Peripheral blood mononuclear cells were stimulated by the gamma-irradiated autologous lymphoblastoid cell line (LCL) and 3 days later seeded into agarose. Colonies were harvested, amplified by addition of interleukin-2 (IL-2), and analysed for T-cell markers and specificity in 51Cr-release assays. Twenty-two colonies were studied: all colonies were OKT3+, five were predominantly OKT4+, 9 were OKT8+ and 8 were mixtures. As expected from previous work, the OKT8+ colonies were cytotoxic for the autologous LCL target and cytotoxicity was blocked by monoclonal antibody (W6/32) to the nonpolymorphic determinants of HLA-A,B,C antigens. Significantly, the OKT4+ colonies tested also showed specific cytotoxicity, but lysis of the autologous LCL was blocked by the monoclonal antibody (OKlal) to the non-polymorphic determinants of HLA-DR antigens. Two interesting patterns of specificity were seen in cytotoxicity tests on sibling LCL targets. In one pattern, targets bearing the A11, B5, DR7 haplotype were lysed, while those bearing the A1, B8, DR3 were not, indicating haplotype preference. In the other pattern, there was lysis of the autologous cell line but not of the sibling targets. These results including HLA-DR-associated restriction, haplotype preference and strict self-preference, further illustrate the complexity of the EBV-cytotoxic T-cell response.

Epstein-Barr virus genome-positive Burkitt's lymphoma is endemic in Africa and Papua New Guinea and in both countries the tumour is restricted to regions with holoendemic malaria. The present work has compared groups of healthy indigenous individuals living in malarious and non-malarious regions of Papua New Guinea for Epstein-Barr virus-specific T-cell-mediated immunity using the in vitro regression assay. Residents of the malarious region (55 tested), when compared with either residents of the non-malarious area (35 tested) or Caucasian controls (27 tested) showed a significant (p less than 0.0001) impairment of virus-specific T-cell immunity but no obvious disturbance (p greater than 0.05) of anti-viral antibody titres. These results may be important in explaining the postulated role of malarial infection as a co-factor in the pathogenesis of Burkitt's lymphoma.

There is a substantial body of evidence suggesting an association between Epstein-Barr virus (EBV) and undifferentiated nasopharyngeal carcinoma (NPC). The present study has compared a group of NPC patients (newly diagnosed and long-term survivors) and controls for EBV-specific T-cell immunity using the regression of transformation assay. Newly diagnosed patients (17 tested) when compared with either long-term survivors (20 tested) or controls (30 tested) showed a significant impairment in virus-specific T-cell immunity (p = 0.036, p = 0.043 respectively). Furthermore, donors with IgA antibody to EBV showed a significant depression in virus-specific T-cell immunity compared with donors without IgA antibody (19 IgA-positive, 48 IgA-negative; p = 0.0025). These results may be important in explaining the postulated role of EBV in the aetiology of NPC.

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Summary The level of Epstein‐Barr virus (EBV)‐specific T‐cell‐mediated immunity in 20 rheumatoid arthritis (RA) patients was compared with 16 age‐and sex‐matched osteoarthritis (OA) patients using the regression of EBV‐transformation assay. The results show that the level of EBV‐specific T‐cell immunity in RA patients is significantly depressed compared with OA patients (P<.001) or healthy laboratory controls (P<.001). In contrast, lymphocytes from RA and OA patients showed a similar ability to act as a responder population in the mixed leucocyte reaction. It is unlikely that the difference in EBV‐specific immunity is due to a general T‐cell defect in RA patients since there was no correlation between EBV‐specific T‐cell immunity and mixed leucocyte reactivity. There was no correlation between EBV‐specific T‐cell immunity and any of the indicators of disease activity nor was there any difference in the anti‐EBV antibody titre between both groups of patients. These results indicate that RA patients are deficient in the EBV‐specific cytotoxic T‐cell precursor population and may explain some of the reported observations of the involvement of EBV in this disease.