Regulatory ripples

Abstract

Regulatory T cells come in many different forms depending on their mode of action or developmental origin. Data now show that interleukin 35, an immunomodulatory cytokine secreted by regulatory T cells, and interleukin 10 induce so-called 'iTR35 cells', which may have an important role in the phenomenon of infectious tolerance.

Figure 1. Regulatory networks

Foxp3⁺ nT_reg cells can control effector responses via various mechanisms, including the release of cytokines such as IL-10, TGF-β and IL-35 or cell surface molecules such as CD39 and CTLA-4. Molecules able to induce T_reg cells, such as regulatory cytokines (IL-10 or TGF-β) or metabolites (retinoic acid), can also be produced by other cell subsets from the surrounding microenvironment. These molecules can contribute to the induction of a new population of T_reg cells, such as iT_reg cells, Tr1 cells or iT_R35 cells. These cells in turn directly or indirectly contribute to the expansion of the regulatory network by inducing new populations of T_reg cells via the process of infectious tolerance. In particular, iT_R35 cells, through their ability to release IL-35, may be able to induce a new population of iT_R35 cells. Foxp3⁺ nT_reg cells and iT_reg cells can also manipulate antigen-presenting cells in a way that renders these cells less efficient at inducing a new population of effector cells or reactivating them. Nrp-1, neuropilin 1; Lag3, lymphocyte-activation gene 3.