Abstract
Naïve CD8+ T cells differentiate into effectors secreting various cytokines that modulate immune functions. A striking finding for most HIV-1–infected patients is that they accumulate CD8+ T cells belonging to early and intermediate differentiated elements. Structural HIV-1 proteins, and among these the matrix protein p17, have been associated with loss of functional competence by different immune cells. We therefore evaluated the influence of p17 on naïve CD8+ T-cell activation and maturation. Anti-CD3 mAb preactivation and subsequent IL-2 stimulation are able to drive human naive CD+ T cells to an effector phenotype characterized, among other features, by downregulation of the co-stimulatory molecule CD28. Strikingly, however, IL-2–induced downmodulation of CD28 was completely prevented by p17, and cells derived from p17-stimulated cultures showed a strong Tc1 polarization that was fourfold higher than that observed in IL-2–stimulated cultures.Moreover, p17 preserved a markedly high proportion of CD8+ T cells that were able to respond to CD28 triggering with a proinflammatory cytokine storm. Our evidence suggests that p17 has important effects on cytokine polarization and phenotype of terminally differentiated CD8+ T cells, and that new p17-based therapeutic approaches could control or prevent HIV-1–related immune disorders.