A CD8?- Subset of CD4+SLAMF7+ Cytotoxic T Cells Is Expanded in Patients With IgG4-Related Disease and Decreases Following Glucocorticoid Treatment.

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 CD8?, 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 ?- and ?-chain gene was performed on circulating CD4+ CTLs from patients with IgG4-RD before and after treatment and in affected tissues. RESULTS:Circulating CD4+ TEM and TEMRA cells were not expanded in IgG4-RD patients compared to healthy controls. CD4+SLAMF7+ TEM cells (but not TEMRA cells) were significantly increased among IgG4-RD patients. Within CD4+SLAMF7+ TEM cells, CD8?- cells but not CD8?low cells were elevated in IgG4-RD patients. The same dominant clones of CD8?-CD4+SLAMF7+ TEM cells found in peripheral blood were also identified in affected tissue. CD8?- and CD8?low CD4+SLAMF7+ TEM cells both expressed cytolytic molecules. Clonally expanded CD8?- but not CD8?low CD4+SLAMF7+ TEM cells decreased following glucocorticoid-induced disease remission. CONCLUSION:A subset of CD8?-CD4+SLAMF7+ cytotoxic TEM cells is oligoclonally expanded in patients with active IgG4-RD. This TEM cell population contracts following glucocorticoid-induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention.

SUBMITTER: Della-Torre E 

PROVIDER: S-EPMC6019645 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature