Dynamics of cytomegalovirus (CMV)-specific T cells in HIV-1-infected individuals progressing to AIDS with CMV end-organ disease.

Abstract

BackgroundSince cytomegalovirus (CMV) infection can cause serious clinical complications in immunocompromised individuals, we assessed cellular immune requirements for protection against CMV end-organ disease (CMV-EOD) in human immunodeficiency virus type 1 (HIV-1) infection MethodsLongitudinal samples from HIV-1–infected patients in the Amsterdam cohort were analyzed. Dynamics of CMV-specific CD8+ and CD4+ T cell responses were analyzed by 4-color fluorescence analysis using major histocompatibility class I CMV peptide-tetramers and by intracellular staining for perforin, granzyme B, and interferon (IFN)–γ after stimulation with CMV-specific stimuli. CMV load was measured in parallel ResultsIn individuals progressing to acquired immunodeficiency syndrome with CMV-EOD, CMV-specific IFN-γ–producing CD4+ T cells disappeared during the year before onset of CMV-EOD. This disappearance was accompanied by a sharp increase in CMV load before onset of disease. Despite increasing CMV-specific CD8+ T cell counts, decreasing CMV-specific IFN-γ–producing CD8+ T cell counts were found over time. In contrast, the percentage of CMV-specific perforin- and granzyme B–expressing CD8+ T cells increased ConclusionsOur data indicate that insufficient help of CD4+ T cells may cause loss of IFN-γ–producing CD8+ T cells and loss of control of CMV dissemination. Increasing CMV-infected cell counts in the face of high CMV-specific perforin- and granzyme B–expressing CD8+ T cell counts may explain the immune pathological characteristics of CMV disease.