A CD8α− Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment

E Della-Torre, E Bozzalla-Cassione, C Sciorati, E Ruggiero, M Lanzillotta, S Bonfiglio, H Mattoo, CA Perugino, E Bozzolo, L Rovati, PG Arcidiacono, G Balzano, D Lazarevic, C Bonini, M Falconi, JH Stone, L Dagna, S Pillai, AA Manfredi

Research output: Contribution to journalArticle

Abstract

Objective: An unconventional population of CD4+ signaling lymphocytic activation molecule family member 7–positive (SLAMF7+) cytotoxic effector memory T (TEM) cells (CD4+ cytotoxic T lymphocytes [CTLs]) has been linked causally to IgG4-related disease (IgG4-RD). Glucocorticoids represent the first-line therapeutic approach in patients with IgG4-RD, but their mechanism of action in this specific condition remains unknown. We undertook this study to determine the impact of glucocorticoids on CD4+ CTLs in IgG4-RD. Methods: Expression of CD8α, granzyme A, perforin, and SLAMF7 within the effector memory compartment of CD45RO+ (TEM) and CD45RA+ effector memory T (TEMRA) CD4+ cells was quantified by flow cytometry in 18 patients with active IgG4-RD, both at baseline and after 6 months of glucocorticoid treatment. Eighteen healthy subjects were studied as controls. Next-generation sequencing of the T cell receptor α- and β-chain gene was performed on circulating CD4+ CTLs from patients with IgG4-RD before and after treatment and in affected tissues. Results: Circulating CD4+ TEMand TEMRAcells were not expanded in IgG4-RD patients compared to healthy controls. CD4+SLAMF7+ TEMcells (but not TEMRAcells) were significantly increased among IgG4-RD patients. Within CD4+SLAMF7+ TEMcells, CD8α− cells but not CD8αlowcells were elevated in IgG4-RD patients. The same dominant clones of CD8α−CD4+SLAMF7+ TEMcells found in peripheral blood were also identified in affected tissue. CD8α− and CD8αlowCD4+SLAMF7+ TEMcells both expressed cytolytic molecules. Clonally expanded CD8α− but not CD8αlowCD4+SLAMF7+ TEMcells decreased following glucocorticoid-induced disease remission. Conclusion: A subset of CD8α−CD4+SLAMF7+ cytotoxic TEMcells is oligoclonally expanded in patients with active IgG4-RD. This TEMcell population contracts following glucocorticoid-induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention. © 2018, American College of Rheumatology
Original languageEnglish
Pages (from-to)1133-1143
Number of pages11
JournalArthritis and Rheumatology
Volume70
Issue number7
DOIs
Publication statusPublished - 2018

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