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Objective An unconventional population of CD 4+ signaling lymphocytic activation molecule family member 7–positive ( SLAMF 7+) cytotoxic effector memory T ( T EM ) cells ( CD 4+ cytotoxic T lymphocytes CTL s) 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 CD 4+ CTL s in IgG4‐ RD . Methods Expression of CD 8α, granzyme A, perforin, and SLAMF 7 within the effector memory compartment of CD 45 RO + ( T EM ) and CD 45 RA + effector memory T ( T EMRA ) CD 4+ 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 CD 4+ CTL s from patients with IgG4‐ RD before and after treatment and in affected tissues. Results Circulating CD 4+ T EM and T EMRA cells were not expanded in IgG4‐ RD patients compared to healthy controls. CD 4+ SLAMF 7+ T EM cells (but not T EMRA cells) were significantly increased among IgG4‐ RD patients. Within CD 4+ SLAMF 7+ T EM cells, CD 8α− cells but not CD 8α low cells were elevated in IgG4‐ RD patients. The same dominant clones of CD 8α− CD 4+ SLAMF 7+ T EM cells found in peripheral blood were also identified in affected tissue. CD 8α− and CD 8α low CD 4+ SLAMF 7+ T EM cells both expressed cytolytic molecules. Clonally expanded CD 8α− but not CD 8α low CD 4+ SLAMF 7+ T EM cells decreased following glucocorticoid‐induced disease remission. Conclusion A subset of CD 8α− CD 4+ SLAMF 7+ cytotoxic T EM cells is oligoclonally expanded in patients with active IgG4‐ RD . This T EM cell population contracts following glucocorticoid‐induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention.
Della‐Torre et al. (Fri,) studied this question.