Exogenous IL-2 Controls the Balance in Th1, Th17, and Treg Cell Distribution in Patients with Progressive Rheumatoid Arthritis Treated with TNF-Alpha Inhibitors

• Published in: Inflammation 2015-04, Vol.38 (2), p.765-774
• Main Authors: Kosmaczewska, Agata, Ciszak, Lidia, Swierkot, Jerzy, Szteblich, Aleksandra, Kosciow, Katarzyna, Frydecka, Irena
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Disease Progression; Humans; Immunology; Interleukin-2 - immunology; Interleukin-2 - pharmacology; Internal Medicine; Middle Aged; Pathology; Pharmacology/Toxicology; Rheumatology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Th17 Cells - drug effects; Th17 Cells - immunology; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-014-9987-x

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.