Potential role of CC chemokine receptor 6 in prediction of late-onset cytomegalovirus infection following solid organ transplant

CCR6 is a chemokine receptor involved in homing memory T cells, particularly Th17 cells, to sites of mucosal inflammation. Despite the critical role of memory T cells in long-term protective immunity against cytomegalovirus (CMV), a virus that reactivates at multiple mucosal sites, the ability of CCR6 or other Th17 marker expression to predict CMV reactivation following transplantation is not clear. Using 11-color flow cytometry, in this prospective single-center pilot study, we measured the expression of CCR6 and other markers of T-cell function in peripheral blood samples obtained from 21 SOT recipients at the time of discontinuation of anti-CMV prophylaxis. CMV viremia was monitored on a monthly basis after discontinuation of prophylaxis. Eleven patients (52%) developed CMV viremia during the six-month follow-up period. Late-onset CMV infection was preceded by an immune phenotype characterized by increased CCR6 expression on bulk CD4⁺ T cells and a reduced number of circulating CMV IE-1-specific Th1 (CD4⁺ IFN-γ⁺) cells. Among the markers evaluated, CCR6 was the best single predictor of late-onset CMV infection. Our results suggest that CCR6 expression at the time of discontinuation of antiviral prophylaxis might be a useful predictor of late-onset CMV reactivation and provide the basis for future larger prospective studies.