Analysis of the structure and dynamics of synaptic interface revealed functional anomaly of naive CD8+ T cells during HIV infection

Abstract

Abstract While it is thought that HIV infection leads to a global defect in T cells, effect of the infection on the T cells at various differentiation stages has not been studied. We have exposed freshly isolated polyclonal CD8 T cells at various differentiation stages to planar lipid bilayers that display anti-CD3 antibody and soluble ICAM-1 and analyzed morphology and dynamics of the synaptic interface formation by the T cells, parameters that are linked to their functional activities. We have found that a large fraction of purified naïve CD8 T cells from HIV-infected people developed mature synapses exhibiting atypical degranulation capacity. These data provide evidence that even at the earlier stages of differentiation CD8 T cells derived from HIV-infected patients reveal functional anomaly causing changes in the ability to degranulate. The latter mediated by aberrant functioning of integrins and actin cytoskeleton resulting from continuous inflammation during chronic HIV infection. Functional anomaly of naïve T cells further impairs functions of CD8 T cells at later differentiation stages contributing to a global defect in T cells and failure to control the infection.