Induction of Human CD8+FoxP3+ Tregs by anti-CD3 mAb
Professor Michael Ehrenstein
Description of Project/Background:
The use of anti-CD3 monoclonal antibody (mAb) for the treatment of type 1 diabetes mellitus and prevention of transplant rejection has been well studied and linked with the induction of regulatory T cell (Treg) populations in vivo. Based on observations made in a mouse model of rheumatoid arthritis (RA) that anti-CD3 therapy can suppress collagen-induced arthritis (CIA) by Notley et al (2010), the aim is to understand its immunomodulatory capacity in the context of RA. Suppression of CIA was associated with the induction of CD8+Foxp3+ T cells that were capable of regulating Th1 and Th17 responses.
CD8+Foxp3+ T cells constitute less than 1% of peripheral CD8+ T cells in healthy and RA patients; therefore, very little is known about their induction or ability to regulate immune responses. Weak stimulation of PBMC (peripheral blood mononuclear cells) from RA patients with anti-CD3 mAb has been found to induce CD8+Foxp3+ T cells which express stable and high levels of CD25 (after 5 days of co-culture with anti-CD3 mAb) and have a similar phenotype to CD4+ Tregs.
Anti-CD3 therapy is also about to enter clinical trials for use in RA; however, it is unknown if it has tolerogenic effects in other rheumatological diseases, notably psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE).