Functional anomaly of CD8 T cells at earlier differentiation stages during HIV infection as established by analysis of synaptic interface and degranulation pattern

Abstract

Abstract It is thought that HIV infection could lead to a global defect in CD8+ T cell function. However, the effect of the infection on CD8+ T cells at various stages of differentiation has not been well studied. To evaluate the functional activity of CD8+ T cells from HIV infected people at various differentiation stages, we assessed their ability to form synaptic interfaces using planar lipid bilayers containing anti-CD3 antibody and soluble ICAM-1 ligand. We analyzed the dynamics of the T cell/bilayer interface formation, size of adhesion area, and kinetics of T-cell degranulation, parameters that are linked to the efficiency of CD8+ T cell functional activity. Unexpectedly, we observed that purified naïve CD8+ T cells (TN) and transitional memory (TTM) from HIV-infected individuals developed mature synapses whereas the same subsets from HIV uninfected individuals did not. While the kinetics of degranulation of naïve T cells was slower, both TN and TTM cells reached a similar extent of degranulation. The fraction and kinetics of CD27-CD45RO+ T cell degranulation were similar to that observed for TTM cells. Treatment with ART led to increase in the fraction of degranulating CD27-CD45RO+ T cells. As opposed to memory cells from healthy donors, a sizable fraction of CD27-CD45RO+ T cells from infected individuals develop lamellopodia and a larger adhesion area after synapse formation. These data suggest that less differentiated CD8+ T cells from HIV-infected people revealed functional anomaly that is likely mediated by aberrant functions of integrins and cytoskeleton causing changes in T-cell plasticity as a result of continuous inflammation during chronic HIV infection.