A subset of CD4+CD8α- Cytotoxic T cells is expanded in patients with IgG4-Related type 1 autoimmune pancreatitis and decreases with glucocorticoid treatment

Context. Type 1 autoimmune pancreatitis (AIP) represents the most frequent manifestation of IgG4 Related Disease (IgG4RD), a systemic fibro-inflammatory condition that promptly responds to glucocorticoids. A population of effector memory CD4+ T cells (Tem) expressing SLAMF7 known as “CD4+ cytotoxic T cells” (CTLs) has been recently implicated in the pathogenesis of IgG4RD-AIP but the effects of glucocorticoids on CD4+CTLs remain unknown. Objective. To describe the impact of glucocorticoids on CD4+CTLs in patients with IgG4RD-AIP. Methods. Eighteen patients with biopsy proven active untreated IgG4-RD were studied at baseline and after 6 months of prednisone. IgG4-RD activity was assessed by means of the IgG4-RD responder index (RI). Flow cytometry on peripheral blood was performed to analyse circulating Tem cells and CD4+CTLs subpopulations. CD4+CTLs have been further analysed for their CD8α expression. Eighteen healthy age- and sex-matched subjects were used as controls (HC). Results. Twelve patients of our cohort (66% of cases) had IgG4RD-AIP. Tem cells were not expanded in patients compared to HC. CD8α- but not CD8α+ SLAMF7+CD4+CTLs were expanded in patients with active untreated IgG4RD compared to HC (p=0.0008 and p>0.05, respectively). After 6 months of therapy with prednisone 15 patients achieved complete remission and 3 patients partial remission. In all patients only the CD8α- population of CD4+CTLs decreased together with clinical improvement compared to baseline values (p=0.001), reaching levels comparable to HC. CD8α+CD4+CTLs and total Tem cells were not affected by glucocorticoid therapy. Conclusions. A subset of CD8α-CD4+CTLs is specifically expanded in patients with IgG4RD-AIP and selectively decreases following therapy with corticosteroids. CD8α-CD4+CTLs represents a potentially novel T cell population implicated in IgG4RD-AIP pathogenesis.