Expression of inhibitory receptors on T cells as marker of disease activity and potential target for immune intervention in Rheumatoid Arthritis.

ONOFRIO LI; ZACCA ER; FERRERO P; ACOSTA C; MUSSANO E; ONETTI L; CADILE I; GAZZONI MV; JURADO R; TOSELLO BOARI J; RAMELLO MC; MONTES CL; GRUPPI A; ACOSTA RODRIGUEZ EV

Arthritis and Rheumatology

Wiley Online Library

Año: 2018

2326-5205

Objective: Inhibitory receptors (IRs) are essential to regulate effector immune responses and may play critical roles during autoimmune diseases. In Rheumatoid Arthritis (RA), we evaluated whether IR expression on T cells showed correlation with immune activation, disease activity and response to treatment as well as if IR-mediated pathways were functional. Methods: By flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from blood and synovial fluid of RA patients ex vivo and after culture. All the parameters were correlated with disease activity score (DAS28) and response to treatment. Results: In RA patients with low activation of T cells, IRs expression showed an inverse relationship with DAS28. Frequencies of T cells expressing multiple IRs were reduced in untreated RA patients but recovered normal levels in treated patients. RA patients that responded to treatment, showed augmented frequency of IRs-expressing T cells that correlated with reduced inflammatory cytokine production in comparison to non-responders. Synovial fluid was enriched in effector and memory T cells expressing multiple IRs. Remarkably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from non-responder patients were less sensitive to inhibition.Conclusion: IR expression on T cells from RA patients inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.