CD8+ T-lymphocyte activation in HIV-1 disease reflects an aspect of pathogenesis distinct from viral burden and immunodeficiency

The CD8(+) T-cell response is central to control and eventual elimination of persistent viral infections. Although it might be expected that CD8(+) T-cell activation would be associated with a better clinical outcome during viral infections, in lone-term HIV-1 infection, high levels of CD8(+) T-cell activation are instead associated with faster disease progression. In this study, cell surface expression of CD38, a flow cytometric marker of T-cell activation of CD8(+) T cells, had predictive value for HIV-1 disease progression that was in part independent of the predictive value of plasma viral burden and CD4(+) T-cell number. Measurements of CD38 antigen expression on CD8(+) T cells in HIV-1-infected patients may be of value for assessing prognosis and the impact of therapeutic interventions, The pathogenetic reason why CD8(+) T-cell activation is associated with poor outcome in HIV-1 disease remains unknown. Possibly CD8(+) T-cell activation contributes to immunologic exhaustion, hyporesponsiveness of T cells to their cognate antigens, or perturbations in the T-cell receptor repertoire.