Abstract
BackgroundAlthough evidence exists that regulatory T cells (Tregs) can suppress the effector phase of immune responses, it is clear that their major role is in suppressing T cell priming in secondary lymphoid organs. Recent experiments using two photon laser microscopy indicate that dendritic cells (DCs) are central to Treg cell function and that the in vivo mechanisms of T cell regulation are more complex than those described in vitro.Principal FindingsHere we have sought to determine whether and how modulation of Treg numbers modifies the lymph node (LN) microenvironment. We found that pro-inflammatory chemokines—CCL2 (MCP-1) and CCL3 (MIP-la)—are secreted in the LN early (24 h) after T cell activation, that this secretion is dependent on antigen-specific DC–T cell interactions, and that it was inversely related to the frequency of Tregs specific for the same antigen. Furthermore, we demonstrate that Tregs modify the chemoattractant properties of antigen-presenting DCs, which, as the frequency of Tregs increases, fail to produce CCL2 and CCL3 and to attract antigen-specific T cells.ConclusionsThese results substantiate a major role of Tregs in LN patterning during antigen-specific immune responses.
Highlights
The immune system has developed several sophisticated regulatory mechanisms that ensure tolerance towards self-antigens and moderate inflammation induced by pathogens and environmental insults
These results substantiate a major role of Tregs in lymph node (LN) patterning during antigen-specific immune responses
The number of total CD8+ T cells at day 2 was significantly increased in the draining LNs (dLNs) of stg mice (Fig. 2E). These results suggest that, in the presence of a high frequency of Tregs, recruitment of dendritic cells (DCs) and lymphocytes to the dLN is decreased during the initial phases of the immune response
Summary
The immune system has developed several sophisticated regulatory mechanisms that ensure tolerance towards self-antigens and moderate inflammation induced by pathogens and environmental insults. Among these mechanisms, suppression of T cell functions by regulatory T cells (Treg) is crucial and Tregs are considered as the primary mediators of peripheral tolerance. It is of obvious importance to define the mechanisms of in vivo T cell regulation, to better understand the process of peripheral tolerance and to develop effective approaches for the clinical manipulation of Treg cells. Evidence exists that regulatory T cells (Tregs) can suppress the effector phase of immune responses, it is clear that their major role is in suppressing T cell priming in secondary lymphoid organs. Recent experiments using two photon laser microscopy indicate that dendritic cells (DCs) are central to Treg cell function and that the in vivo mechanisms of T cell regulation are more complex than those described in vitro
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