Detection of different virus-specific CD8+ T cells after kidney transplantation

BACKGROUND: The early diagnosis of viral reactivation after kidney transplantation (KTX) is an unsolved problem. Survey of virus-specific T-cell responses may identify patients at risk for viral reactivation. We therefore quantified virus-specific CD8+ T-cells to evaluate their potential predictive value for viral reactivation and infection in KTX patients.

METHODS: We quantified the virus-specific responses of CD8+ T-cells for CMV, EBV, HPV and HHV in 23 patients undergoing KTX for 6 mo after transplantation. We enumerated T-cells for 36 virus-specific binding peptides and five different human leukocyte antigen (HLA) alleles through the binding of Class I iTAg major histocompatibility complex (MHC) tetramers. The patients' pre-operative serologic status for CMV and CMV-specific CD8+ T-cell numbers were correlated with one another (p=0.0046).

RESULTS: Three patients had clinical CMV disease and all three remained or became CMV-tetramer-positive for at least one HLA allele during follow-up. Three of the four patients with viral infections caused by or reactivations of viruses other than CMV were initially negative for CMV-specific CD8+ T-cells but became CMV-positive. Most of the patients who were initially CMV-tetramer positive also had tetramer-positive T-cells specific for Epstein-Barr virus (EBV); human papillomavirus (HPV)-6b, -11, -16, or -18; or human herpesvirus (HHV)-8. All of the patients who developed viral disease other than that caused by CMV remained or became positive for at least one binding peptide that was specific for a virus not directly related to the clinical features of a viral disease.

CONCLUSION: Patients who were positive for any virus had a significantly greater risk of developing complications of viral disease during the 6-mo follow-up period in the study (p=0.026), suggesting a general susceptibility to viral reactivation. The evaluation of virus-specific CD8+ T-cells may prospectively help to identify patients at risk for viral reactivation after KTX.