Increased proportions of activated and proliferating memory CD8+ T lymphocytes in both blood and lung are associated with blood HIV viral load

Abstract

One mechanism of HIV pathogenesis has been proposed to be the activation of T lymphocytes, resulting in proliferation and decreased survival of these activated cells. Others have suggested that co-infections may exacerbate this process. These hypotheses were tested by examining the relationship between HIV blood viral load with the proportion of activated and proliferating CD8+ lymphocytes in lung and blood. In the lung these responses were compared in patients with or without respiratory pathogens. Thirty-five HIV-positive patients and five controls underwent bronchoalveolar lavage (BAL). BAL and blood samples were fixed and permeabilized and the proportions of memory CD8+ lymphocytes that expressed the activation marker CD38 and the cell cycling marker Ki67 were measured by flow cytometry. CD38bright CD8+ lymphocytes from both sites increased with increasing blood viral load. In BAL there was no significant difference between the CD38 activation status in those with respiratory pathogens compared with those without. More CD38bright CD8+ lymphocytes expressed Ki67 when compared with the CD38dim lymphocytes. These findings provide evidence that HIV is the primary factor in stimulating CD8+ cell activation.