Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates with markers of disease severity and changes towards normalization under treatment

Abstract

The relationship between blood CD8+ T lymphocyte subsets, as defined by CD28 and CD38 expression, and plasma viraemia and CD4+ T cells in HIV-1 infection was investigated. In a cross-sectional study of 46 patients with either no or stable anti-retroviral treatment, there was a strong negative correlation between the percentage of CD8+CD28- and the percentage of CD4+ T cells (r=-0.75, P<0.0001), and a positive correlation between absolute numbers of CD8+CD28+ and CD4+ T cells (r=0.56, P<0.0001). In contrast, the expression of CD38 by CD8+ T lymphocytes correlated primarily with plasma viraemia (e.g. the percentage of CD38+ in CD8(bright) cells, r= 0.76, P< 0.0001). In the 6 months following triple therapy initiation in 32 subjects, there was a close correlation between changes (Δ) in CD8+CD28+ or CD8+CD28- and in CD4+ T cells (e.g. Δ% CD8+CD28+ versus Δ% CD4+, r=0.37, P=0.0002; Δ% CD8+CD28-versus Δ% CD4+, r=-0.66, P<0.0001). A marked decline of the number of CD8+ T cells expressing CD38 was also observed. These results suggest the existence of a T cell homeostasis mechanism operating in blood with CD4+ and CD8+CD28+ cells on the one hand, and with CD8+CD28- cells on the other. In addition, the percentage of CD38+ cells in CD8+ cells, generally considered an independent prognostic factor, could merely reflect plasma viral load.