Analysis and application of anti-herpesviuses immunity among organ recipients by use of MHC-tetramers.

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Background : Organ recipients are at risk of herpes viruses infection, including cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Cytotoxic T-cells (CTL) are the pivotal component to control these viral infections. Tetrameric HLA (so-called tetramers) detect specific CTL against these viruses, and may help future adoptive therapy.Aim : To evaluate tetramers as agents for monitoring CTLs, and to isolate and expand specific CTL for possible therapeutic purpose.Methods : Sixty recipients of living liver graft were prospectively followed for 2-48 months. All had either of HLA A*0201 or A*2402, and corresponding tetramers were used to stain CTL. Viral DNA were monitored by real-time PCR. Samples with high viral load were assigned for isolation of specific CTLs by tetramers, and were incubated for expansion.Results : A*0201 CMV pp65 tetramer detected CTL more efficiently than A*2402 CMV pp65 tetramer, even though the frequency of CMV infection was similar in both of A*0201 recipients and A*2402 recipients. In the presence of CMV DNAemia, A*0201 CMV pp65 tetramer found CTL in 100% of recipients, whereas only 46% in case of A*2402 CMV pp65. Severity of infection was similar irrespective of CTL detection by tetramers. Similar results were obtained for EBV.Expansion of CTL failed although the amounts of CTL were higher when viral loads were high.Interpretation : Tetrameric HLA detects only a part of whole anti-viral CTL, which makes it difficult to apply tetramer detection of CTL for predictor of infection prognosis. Isolation of specific CTL failed partly due to scarcity of appropriate samples. An analysis of risk factors of CMV infection was done to add a new point of view for prognosis of infection.