Survival and Proliferation of CD28 super(-) T Cells During HIV-1 Infection Relate to the Amplitude of Viral Replication

• Published in: The Journal of infectious diseases Vol. 203; no. 11; pp. 1658 - 1667
• Main Authors: Vivar, Nancy, Ruffin, Nicolas, Sammicheli, Stefano, Hejdeman, Bo, Rethi, Bence, Chiodi, Francesca
• Format: Journal Article
• Language: English
• Published: 01.06.2011
• Subjects: Human immunodeficiency virus 1
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir156

Background. CD28 super(-) T lymphocytes progressively increase during aging, autoimmunity, and HIV-1 infection. Expansion of these cells stands in contrast with their senescent phenotype described by several studies. Understanding the functional properties and phenotype of CD28 super(-) T cell during HIV-1 infection is important, because this subset incorporates T cells specific for HIV-1 and other chronic pathogens. Methods. Blood samples were obtained from 23 healthy and 43 HIV-1-infected individuals: 26 receiving antiretroviral therapy and 17 naive to treatment. The phenotype of CD28 super(-) and CD28 super(+) T cells was determined by flow cytometry. T cells were activated through T-cell receptor before apoptosis and proliferation measurements. Interleukin (IL)-2, tumor-necrosis factor, interferon-c, and perforin production were analyzed using enzyme-linked immunosorbent assay. Results. CD28 super(-) T cells from patients receiving antiretroviral therapy exhibited a low sensitivity to apoptosis and enhanced proliferation after TCR stimulation, compared with T cells of uninfected individuals. On the contrary, CD28- T cells from viremic patients showed a decreased Bcl-2 expression, a high sensitivity to apoptosis, and poor proliferative ability, compared with treated patients and control subjects. T cells from untreated patients produced less IL-2, possibly underlying their decreased proliferative abilities. Conclusions. The level of HIV-1 replication and associated immunoactivation represent a critical factor in regulating survival and activation of CD28 super(-) T cells.