CD8(+) lymphocyte phenotype and cytokine production in long-term non-progressor and in progressor patients with HIV-1 infection

In most HIV-1-infected patients, clinical and immunological progression develops within a few years. Few infected people, termed long-term non-progressors (LTNP), remain healthy and immunologically stable for a long time. The factors governing the maintenance of this condition are not well known, but it is conceivable that CD8(+) lymphocytes, cells that play a central role in controlling in vitro HIV replication, may have a part in vivo in this process. The aim of this study was to characterize the phenotypic profile and the cytokine production of CD8(+) cells in a group of LTNP patients who had stable CD4(+) cell counts (>500/mm(3)) for at least 7 years. Their CD8(+) absolute numbers were similar to a control group composed of HIV-1(+) patients who have a progressive decline of their CD4(+) cell counts. However, our multiparameter immunofluorescence studies show that a clinical and immunologically stable condition is associated with the presence of a CD28(+), CD95 strongly positive CD8(+) population, while disease progression is marked by the CD28(-)CD95(+)CD8(+) subset. Purified CD8(+) cells from LTNP retain their ability to produce IL-2, interferon-gamma (IFN-gamma) and, to a lesser degree, to produce IL-10 and IL-4. In contrast, CD8(+) cells from progressors are unable to secrete IL-2 and IL-10. Although CD8(+) cytokine profile does not fit with the proposed T helper (Th)1/Th2 switch in progressive HIV infection, LTNP CD8(+) T cells maintain their capacity to produce IL-2 and IL-10 (Th0-like), a pattern very similar to that observed in normal HIV healthy controls. We suggest that CD8(+) cells expressing CD28, CD95 and having a Th0-like profile may be considered to be associated with long-term survival.