Characterization of T Cell Subsets Involved in the Production of IFN-γ in Asymptomatic HIV-Infected Patients

Abstract

Cells capable of interferon (IFN)-γ synthesis following mitogenic stimulation can be detected and quantified by a recently developed immunofluorescence assay and flow cytometric analysis. The production of IFN-γ was investigated in a cohort of 20 asymptomatic human immunodeficiency virus (HIV)-seropositive patients with normal numbers of CD4⁺ lymphocytes, and in 10 healthy subjects. About 60% of asymptomatic stage A1 patients had increased percentages of blood lymphocytes capable of IFN-γ synthesis, as compared to healthy subjects. The difference reflected the relatively higher numbers of CD8⁺ cells, in particular the CD8+ T cell subset lacking CD28 antigen expression. The strong correlation between the CD4⁺/CD8⁺ ratio and the CD8⁺CD28⁺/CD8⁺CD28⁻ ratio suggests either a role for CD4⁺ cells in controlling the CD28⁺ phenotype or a role for CD8⁺CD28⁻ cells in the decline of CD4⁺ lymphocytes. The peculiar ability of CD8⁺CD28⁻ cells to produce high amounts of IFN-γ, as compared to CD8⁺CD28⁺ cells, supports the hypothesis that the CD8⁺CD28⁻ lymphocytes constitute a population that is functionally distinct from their double-positive counterparts.