The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection

Abstract

Chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from people living with HIV, here we expose the T cells to planar lipid bilayers containing ligands for T-cell receptor and a T-cell integrins and analyze the cellular morphology, dynamics of synaptic interface formation and patterns of the cellular degranulation. We find a large fraction of phenotypically naive T cells from chronically infected people are capable to form mature synapse with focused degranulation, a signature of a differentiated T cells. Further, differentiation of aberrant naive T cells may lead to the development of anomalous effector T cells undermining their capacity to control HIV and other pathogens that could be contained otherwise.

HIV infection over time is thought to result in premature aging and aberrant immune responses including the induction of immunological senescence. Here the authors show altered formation of immune synapses by naive CD8⁺ T cells and dysregulated synapse functioning at late differentiated stages in people living with HIV.