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. The Swiss HIV Cohort Study

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 CD8bright 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 (delta) in CD8+CD28+ or CD8+CD28- and in CD4+ T cells (e.g. delta % CD8+CD28+ versus delta % CD4+, r = 0.37, P = 0.0002; delta % CD8+CD28- versus delta % 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.

Fig. 1

Changes observed in a representative patient (no. 28) after treatment initiation at day 0. The treatment consisted of stavudine, lamivudine and nelfinavir. In this patient, changes in the percentages of CD4⁺, CD8⁺CD28⁺, CD8⁺C28⁻, CD8^brightCD38⁺ and CD38^brightCD38⁻ T cells among all lymphocytes were quite similar to the corresponding changes in absolute cell numbers and are therefore not depicted.

Fig. 2

Changes in the percentage of CD38⁺ cells among CD8^bright cells, compared with the evolution of plasma viraemia and the increase in the CD4⁺/CD8⁺ ratio. Patient 12 (□) received stavudine, ritonavir and saquinavir, and discontinued treatment on his own initiative after the third visit. Patients 18 (▪) and 19 (○) also received stavudine, ritonavir and saquinavir, and patient 27 (▵) stavudine, lamivudine and ritonavir.