Rescuing CD4+CD25+ regulatory T-cell functions in rheumatoid arthritis by cytokine-targeted monoclonal antibody therapy.
CD4+CD25+ regulatory T cells (Tregs) play a crucial role in controlling the development of autoimmune diseases such as rheumatoid arthritis (RA). However, despite an increased number of Tregs, the persistence of inflammation in the rheumatoid joints suggests that Tregs are unable to suppress ongoing disease, perhaps due to an inhibition of their functions by pro-inflammatory cytokines. Treatment of RA patients with anti-TNF-alpha monoclonal antibodies such as infliximab and adalimumab has been found to induce and restore the functions of Tregs. Thus, manipulation of the pro-inflammatory environment in the inflamed synovia via neutralization of inflammatory cytokines by monoclonal antibodies could represent a novel therapeutic strategy for restoring the suppressive functions of Tregs and induction and/or expansion of Tregs in order to reinforce tolerance mechanisms.
Bayry
Jagadeesh
J
INSERM, UMR S 872, Université Pierre et Marie Curie (UPMC-Paris-6), Equipe 16 "Immunopathology and Therapeutic Immunointervention," Centre de Recherche des Cordeliers, Paris 75006, France. jagadeesh.bayry@umrs681.jussieu.fr
Sibéril
Sophie
S
Triebel
Frédéric
F
Tough
David F
DF
Kaveri
Srini V
SV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D014409:Tumor Necrosis Factor-alpha