Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection

• Published in: The Journal of immunology (1950) 2010-09, Vol.185 (5), p.3007-3018
• Main Authors: Kassu, Afework, Marcus, Roland A, D'Souza, Michelle B, Kelly-McKnight, Elizabeth A, Golden-Mason, Lucy, Akkina, Ramesh, Fontenot, Andrew P, Wilson, Cara C, Palmer, Brent E
• Format: Article
• Language: English
• Subjects: Adult; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Chronic Disease; Cohort Studies; Epitopes, T-Lymphocyte - immunology; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - immunology; HIV-1 - metabolism; Human immunodeficiency virus; Humans; Receptors, Antigen, T-Cell - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000156

Elevated expression of inhibitory receptors on virus-specific T cells has been implicated as a mechanism by which viruses evade host immune surveillance. Blockade of these pathways during chronic infection leads to increased T cell function and improved immune control of viral replication. To explore the association between costimulatory receptors and HIV replication, we examined the expression of programmed death 1 (PD-1), CTLA-4, T cell Ig domain and mucin domain 3 (TIM-3), and CD28 on HIV-specific CD4(+) T cells from HIV-infected subjects. Greater than 30% of HIV-specific CD4(+) T cells from untreated subjects coexpressed PD-1, CTLA-4, and TIM-3, whereas