Author(s):
Duarte, Joana 
; Agua-Doce, Ana ; Oliveira, Vanessa G. ; Fonseca, João Eurico ; Graça, Luís
Date: 2010
Persistent ID: http://hdl.handle.net/10451/6033
Origin: Repositório da Universidade de Lisboa
Subject(s): Rheumatoid arthritis; Th 17; Treg cells; Foxp3; Antigens, CD4
Description
©2010 Duarte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells.
Methodology and Findings: We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice – a recently described animal model of RA – by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60
days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction.
Conclusions: Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG
mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance
towards immune tolerance.
