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  • Title: Dynamics of cytomegalovirus (CMV)-specific T cells in HIV-1-infected individuals progressing to AIDS with CMV end-organ disease.
    Author: Bronke C, Palmer NM, Jansen CA, Westerlaken GH, Polstra AM, Reiss P, Bakker M, Miedema F, Tesselaar K, van Baarle D.
    Journal: J Infect Dis; 2005 Mar 15; 191(6):873-80. PubMed ID: 15717261.
    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 perforin, granzyme B, and interferon (IFN)- gamma 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- gamma -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- gamma -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. CONCLUSIONS: Our data indicate that insufficient help of CD4(+) T cells may cause loss of IFN- gamma -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.
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