Premium
Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis
Author(s) -
Dahlén R.,
Strid H.,
Lundgren A.,
Isaksson S.,
Raghavan S.,
Magnusson M. K.,
Simrén M.,
Sjövall H.,
Öhman L.
Publication year - 2013
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12081
Subject(s) - ulcerative colitis , infliximab , peripheral blood , effector , in vitro , medicine , immunology , peripheral , tumor necrosis factor alpha , biology , disease , biochemistry
Many patients with inflammatory bowel disease ( IBD ) are undergoing therapy with infliximab, an antibody specific for TNF . However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti‐ TNF therapy–naïve ulcerative colitis ( UC ) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA , and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD 25 in CD 4 + and CD 8 + T cell populations and inhibited secretion of IFN ‐γ, IL ‐13, IL ‐17A, TNF as well as granzyme A. Infliximab also suppressed CD 4 + and CD 8 + T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen‐specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP 3 + CD 4 + T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD 25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab‐mediated disease remission in patients with UC .