title: Exogenous IL-2 controls the balance in Th1, Th17, and Treg cell distribution in patients with progressive rheumatoid arthritis treated with TNF-alpha inhibitors.
abstract: Interleukin-2 (IL-2) has been suggested to control Treg/Th17 balance. Recently, we reported a relationship of rheumatoid arthritis (RA) activity/progression with irreversible systemic Treg and Th1 defects including serum IL-2 shortage. Herein, we explore the role of in vitro stimulation with rIL-2 in the observed immune alterations reversal. Patients with stable or progressive RA were assigned to methotrexate (MTX) group or to TNF-alpha inhibitors (iTNF) group, respectively. Flow cytometric analyses were performed before and after 6 months of treatment. Circulating Th1, Th17, and Treg cells were determined before and after 72-h culture with anti-CD3 + rIL-2. Before therapy, 72-h stimulation restored recently observed phenotypic Th cell alterations, except for the enriched Th17 subset normalized as late as after therapy in all patients. Under 6-month therapy, anti-CD3 stimulation changed the Th cell distribution only in progressive RA; despite Th1 enrichment, it revealed Treg population defects, which were completely reversed by exogenous IL-2 added to the stimulating culture. Our paper shows that in aggressive RA patients exhibiting serum IL-2 shortage despite iTNF therapy, exogenous rIL-2 is capable of promoting Treg differentiation affected by chronic activation, thus supporting its use in the combined strategy of biologic treatment of the progressive form of RA.
authors.affiliation: Department of Immunopathology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla St. 12, 53-114, Wroclaw, Poland, kosmacz@iitd.pan.wroc.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Kosmaczewska
authors.forename: Lidia
authors.initials: L
authors.lastname: Ciszak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Swierkot
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Szteblich
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kosciow
authors.forename: Irena
authors.initials: I
authors.lastname: Frydecka
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D018450:Disease Progression; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha