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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Combadière
Béhazine
B
INSERM U543, Laboratoire d'Immunologie Cellulaire, Faculté de Médecine Pitié-Salpêtière, Paris, France.
Faure
Sophie
S
Autran
Brigitte
B
Debré
Patrice
P
Combadière
Christophe
C
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018959:CD57 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D018709:Statistics, Nonparametric; D019562:Viral Load
D018959:CD57 Antigens; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D007371:Interferon-gamma