The chemokine receptor CX3CR1 controls homing and anti-viral potencies of CD8 effector-memory T lymphocytes in HIV-infected patients.

Abstract

We have recently reported that the polymorphism of the fractalkine receptor, CX3CR1, provides a new marker for prognosis in HIV disease. In order to understand the mechanism by which CX3CR1 participates in the regulation of HIV-immune responses, we investigated its expression and role on T lymphocytes in HIV-infected patients. For that purpose, we analysed the expression of CX3CR1 on CD4 and CD8 effector-memory subsets in HIV-positive individuals by flow cytometric analyses, and studied its potential role in the migration and function of CD8 effector cells. We observed an increased frequency of CD8 cells expressing CX3CR1 that was correlated with disease progression in HIV-infected patients compared with normal individuals. CX3CR1+ was expressed mainly on activated and differentiated CCR7-CD45RA-negative memory lymphocytes. Interestingly, CX3CR1 appeared as the main homing receptor of these cells that have downmodulated most other chemokine receptors. The CD8+CX3CR1+ lymphocytes were engaged in the cytotoxic lineage (perforin+, CD27-negative and CD57+). Ex-vivo analysis showed that CX3C ligand-1 inhibits IFNgamma production in response to T cell receptor engagement. CX3CR1 and its ligand could contribute to the specific migratory pattern of late-stage differentiated CD8 cells and participate in the regulation of effector function of CD8 lymphocytes during HIV infection.