Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis

ONOFRIO, LUISINA I.; ACOSTA, CRISTINA; CADILE, ISAAC; BOARI, JIMENA TOSELLO; GRUPPI, ADRIANA; ZACCA, ESTEFANIA R.; MUSSANO, EDUARDO; GAZZONI, M. VICTORIA; RAMELLO, MARIA C.; ACOSTA RODRÍGUEZ, EVA V.; FERRERO, PAOLA; ONETTI, LAURA; JURADO, RAÚL; MONTES, CAROLINA L.; ONOFRIO, LUISINA I.; ACOSTA, CRISTINA; CADILE, ISAAC; BOARI, JIMENA TOSELLO; GRUPPI, ADRIANA; ZACCA, ESTEFANIA R.; MUSSANO, EDUARDO; GAZZONI, M. VICTORIA; RAMELLO, MARIA C.; ACOSTA RODRÍGUEZ, EVA V.; FERRERO, PAOLA; ONETTI, LAURA; JURADO, RAÚL; MONTES, CAROLINA L.

Arthritis & Rheumatology

Wiley

Año: 2018 vol. 70 p. 1429 - 1439

Objective. Inhibitory receptors are essential forthe regulation of effector immune responses and mayplay critical roles in autoimmune diseases. We evaluatedwhether inhibitory receptor expression on T cells frompatients with rheumatoid arthritis (RA) were correlatedwith immune activation, disease activity, and responseto treatment, as well as whether inhibitory receptor?mediated pathways were functional.Methods. Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+and CD8+ T cells from the blood and synovial fluid (SF)of RA patients ex vivo and after culture. The relationshipof each parameter with the Disease Activity Scorein 28 joints using the erythrocyte sedimentation rate(DAS28-ESR) and response to treatment was examined.Results. In RA patients with low levels of T cellactivation, inhibitory receptor expression showed aninverse relationship with the DAS28-ESR. The frequencyof T cells expressing multiple inhibitory receptors wasreduced in untreated RA patients but returned to normallevels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory Tcells that expressed multiple inhibitory receptors wereseen in SF than in peripheral blood. Notably, inhibitorypathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponderpatients were less sensitive to inhibition.Conclusion. Inhibitory receptor expression on Tcells from RA patients is inversely correlated with effector T cell function and disease activity and may predictresponse to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatmentstrategies to regulate acute local inflammation.