Increased Expression of CD69 on T Cells as an Early Immune Marker for Human Cytomegalovirus Reactivation in Chronic Lymphocytic Leukemia Patients

Abstract

Reactivation of human cytomegalovirus (HCMV) remains a serious problem in immunosuppressed individuals. To investigate whether a change in the immune status can be used as an earlier marker for HCMV reactivation than the traditional PCR analysis, eight chronic lymphocytic leukemia (CLL) patients at risk for reactivation due to commencement of alemtuzumab (anti-CD52) treatment were longitudinally followed. Five series of consecutive weekly blood samples were immunophenotyped by flow cytometry to cover both the innate and adaptive immune responses. Concurrently, patients were monitored by PCR for HCMV reactivation. We found a minor upregulation of the early activation marker CD69 on NK cells immediately before HCMV was detected in circulation by PCR. Interestingly, for the specific immune response, CD69 was highly upregulated on CD3⁺ T cells, especially for the CD8⁺ subset, in the two patients experiencing an HCMV reactivation between 6 and 20 d before HCMV viremia was measured by PCR. Moreover, a CD4⁺:CD8⁺ ratio lower than 0.6 may indicate a trend toward an increased risk for viral reactivation. In conclusion, an increase in CD69 expression is a promising candidate as an early predictor of HCMV reactivation.