Human cytomegalovirus (HCMV)-specific CD4+ T lymphocyte response in AIDS patients with no past or current HCMV disease following HAART

Abstract

The incidence of Human Cytomegalovirus (HCMV) end-organ disease has dramatically decreased since the implementation of highly active antiretroviral therapies (HAARTs), but the precise immune mechanism whereby HCMV is controlled remains to be elucidated. To investigate the effect of (HAART) on CD4+ T-cell immunity to HCMV in AIDS patients with no past or current HCMV disease. Seventeen patients were prospectively examined for CD4+ (CD45RO+ and CD45 RA+) T-cell counts (flow cytometry), HIV RNA load (Amplicor HIV test), HCMV leukoDNAemia and HCMV DNA in urine (nested PCR), lymphoproliferative response (LPR) to HCMV, phytohemagglutinin (PHA) and purified protein derived from Mycobacterium tuberculosis (PPD) by measurement of 5-bromo-2'-deoxyuridine incorporation to DNA (ELISA) and cytokine secretion (IFN-gamma, IL-4 and IL-10) by HCMV-stimulated peripheral blood mononuclear cell (PBMC) cultures (ELISA). Fifteen patients responded favorably to HAART (virologically, immunologically, or both). Of these, six patients presented LPR to HCMV at least once during follow-up, whereas most displayed detectable LPRs to PHA. IFN-gamma was detected at least once in supernatants of HCMV-stimulated PBMC cultures from 14 of the 17 patients. All but one patient tested negative for HCMV leukoDNAemia and HCMV DNA in urine, and none developed HCMV disease during the observation period. Control of HCMV replication and the absence of HCMV disease are not consistently associated with recovery and/or maintenance of LPR to HCMV in AIDS patients under HAART and with no prior HCMV disease. Whether detection of IFN-gamma by PBMCs upon HCMV antigenic stimulation may serve as a surrogate marker for protection against HCMV disease requires further investigation.