Decreased 4-1BB expression on HIV-specific CD4+ T cells is associated with sustained viral replication and reduced IL-2 production

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2009-08, Vol.132 (2), p.234-245
• Main Authors: Kassu, Afework, D'Souza, Michelle, O'Connor, Brian P, Kelly-McKnight, Elizabeth, Akkina, Ramesh, Fontenot, Andrew P, Palmer, Brent E
• Format: Article
• Language: English
• Subjects: 4-1BB expression; 4-1BB Ligand - biosynthesis; Allergy and Immunology; Analysis of Variance; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; CMV-specific CD4+ T cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; Flow Cytometry; Fluorescent Antibody Technique; HIV Infections - blood; HIV Infections - immunology; HIV Infections - metabolism; HIV-specific CD4+ T cells; Human immunodeficiency virus; Humans; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Monocytes - immunology; Monocytes - metabolism; Monocytes - virology; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Cells - virology; OX40 expression; OX40 Ligand - biosynthesis; Receptors, OX40 - biosynthesis; Tumor Necrosis Factor Receptor Superfamily, Member 9 - biosynthesis; Virus Replication
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.03.531

Abstract CD4+ T cell dysfunction in subjects with chronic HIV infection is in part due to an imbalance of costimulatory and coinhibitory receptors. We report that virus-specific CD4+ T cells expressing 4-1BB (CD137) or OX40 (CD134) produced more IL-2 than cells lacking these costimulatory receptors ( P < 0.05) and that 4-1BB was expressed at a lower level on HIV- than CMV-specific IFN-γ and IL-2 producing CD4+ T cells ( P < 0.0001 and P < 0.01, respectively). Suppression of viral replication with antiretroviral therapy was associated with increased 4-1BB expression on HIV- and CMV-specific IL-2 producing CD4+ T cells ( P < 0.05 and P < 0.01, respectively) and the percentage of IL-2 producing HIV-specific CD4+ T cells that expressed 4-1BB was inversely correlated with HIV plasma viral load ( r = − 0.75, P = 0.007). These findings indicate that the loss of 4-1BB on HIV-specific CD4+ T cells is associated with viral replication and that it may contribute to reduced IL-2 production observed during chronic infection.