Partial restoration of cytokine profile despite reconstitution of cytomegalovirus-specific cell-mediated immunity in human immunodeficiency virus-infected patients during highly active antiretroviral treatment.

Abstract

We reconstituted cytomegalovirus (CMV)-specific T-cell responses in human immunodeficiency virus-1-positive, CMV-positive patients receiving highly active antiretroviral treatment (HAART). We used several combinations of functionality parameters to determine the degree of T-lymphocyte reconstitution obtained during 1 year of treatment. Untreated patients displayed CMV-specific cytotoxic T-lymphocyte (CTL) activity despite the absence of CMV-specific lymphoproliferative responses (LPRs) and despite the fact that interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) were not secreted. The absence of LPRs, IFN-gamma and IL-2 before antiretroviral treatment suggests that CMV-specific immunity was deregulated despite the high CD4+ T-cell counts presented by our cohort, which are critical to the reactivation of CMV disease. After 6 months of HAART, CTL activity had increased compared with the baseline, as had the levels of secreted IFN-gamma and LPR. However, the levels of specific IL-2 produced did not change during therapy, and no specific IL-2 was detected during the follow-up period. Taken together, our findings suggest that 1 year of HAART led to the recovery of some, but not all, CMV-specific responses in our cohort of patients.