HIV-1-Specific Memory CD4+ T Cells Are Phenotypically Less Mature Than Cytomegalovirus-Specific Memory CD4+ T Cells

• Published in: The Journal of immunology (1950) Vol. 172; no. 4; pp. 2476 - 2486
• Main Authors: Yue, Feng Yun, Kovacs, Colin M, Dimayuga, Rowena C, Parks, Paul, Ostrowski, Mario A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.2004
• Subjects: Antiretroviral Therapy, Highly Active; CD28 Antigens - biosynthesis; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Separation; Cytomegalovirus - immunology; Epitopes, T-Lymphocyte - immunology; Flow Cytometry; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Humans; Immunologic Memory - drug effects; Immunophenotyping; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Staining and Labeling; Tumor Necrosis Factor Receptor Superfamily, Member 7 - biosynthesis
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.4.2476

HIV-1-specific CD4(+) T cells are qualitatively dysfunctional in the majority of HIV-1-infected individuals and are thus unable to effectively control viral replication. The current study extensively details the maturational phenotype of memory CD4(+) T cells directed against HIV-1 and CMV. We find that HIV-1-specific CD4(+) T cells are skewed to an early central memory phenotype, whereas CMV-specific CD4(+) T cells generally display a late effector memory phenotype. These differences hold true for both IFN-gamma- and IL-2-producing virus-specific CD4(+) T cells, are present during all disease stages, and persist even after highly active antiretroviral therapy (HAART). In addition, after HAART, HIV-1-specific CD4(+) T cells are enriched for CD27(+)CD28(-)-expressing cells, a rare phenotype, reflecting an early intermediate stage of differentiation. We found no correlation between differentiation phenotype of HIV-1-specific CD4(+) T cells and HIV-1 plasma viral load or HIV-1 disease progression. Surprisingly, HIV-1 viral load affected the maturational phenotype of CMV-specific CD4(+) T cells toward an earlier, less-differentiated state. In summary, our data indicate that the maturational state of HIV-1-specific CD4(+) T cells cannot be a sole explanation for loss of containment of HIV-1. However, HIV-1 replication can affect the phenotype of CD4(+) T cells of other specificities, which might adversely affect their ability to control those pathogens. The role for HIV-1-specific CD4(+) T cells expressing CD27(+)CD28(-) after HAART remains to be determined.