Background: CD28(-) 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(-) 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(-) and CD28(+) 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-γ, and perforin production were analyzed using enzyme-linked immunosorbent assay.
Results: CD28(-) 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(-) T cells.