Summary

Proposed mechanisms of immunosuppression by regulatory T cells include: production of immunosuppressive IL-10, IL-35 and TGFβ (some TGFβ is membrane bound); production of cytolytic granzyme B; TIGIT-mediated DC production of IL-10 and TGFβ; LAG3 mediated down-regulation of DC function; CTLA4 preventing co-stimulation by by CD80 and CD86 through CD28; inducing expression of IDO by DCs; the cell surface ectoenzymes CD39 and CD73 producing immunosuppressive adenosine; starving effector cells of IL2 through high affinity uptake by regulatory T cell IL2 receptors; inducing IL-10 production by non-regulatory T cells. Abbreviations: CD = cluster of differentiation; DC = dendritic cell; IL = interleukin; TGFβ = transforming growth factor beta; IL2R = IL2 receptor; TIGIT = T cell immunoreceptor with Ig and ITIM domains; LAG-3 = lymphocyte-activation gene 3; IDO = indoleamine 2,3-dioxygenase; CTLA4 = cytotoxic T lymphocyte antigen 4; MHCII = major histocompatibility complex II. Adapted from Vignali DAA. et al., (2008) Nature Immunology 8(7)525-532

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