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

Abstract

Background. Since 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. Methods. Longitudinal 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 perform, granzyme B, and Interferon (IFN)-γ after stimulation with CMV-specific stimuli. CMV load was measured in parallel. Results. In 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 perform- and granzyme B-expressing CD8+ T cells increased. Conclusions. Our 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. © 2005 by the Infectious Diseases Society of America. All rights reserved.