TY - JOUR
T1 - Physiologic control of the functional status of Foxp3+ regulatory T cells
AU - Mellor, Andrew L.
AU - Munn, David H.
PY - 2011/4/15
Y1 - 2011/4/15
N2 - Foxp3-lineage CD4 regulatory T cells (Tregs) were named for their ability to maintain self tolerance and suppress T cell immunity. However, resting Tregs from noninflamed tissues exhibit little suppressor activity, and must be stimulated to acquire such function. Conversely, under certain inflammatory conditions, Tregs may undergo rapid reprogramming to acquire helper/effector functions. In this Brief Review, we describe recent progress in elucidating physiologic processes that control the functional status of Foxp3-lineage Tregs. Emerging evidence suggests the surprising possibility that reprogrammed Tregs can be an indispensable source of helper activity in some physiologic settings, such as priming CD8+ T cell responses. This suggests a novel paradigm in which Foxp3+ Tregs intrinsically possess bifunctional potential, acting as a preformed pool of first-responder cells at sites of local inflammation that can either provide classical regulatory/suppressor activity, or rapidly reprogram to supply helper/effector activity, contingent on signals that manifest in local physiologic settings.
AB - Foxp3-lineage CD4 regulatory T cells (Tregs) were named for their ability to maintain self tolerance and suppress T cell immunity. However, resting Tregs from noninflamed tissues exhibit little suppressor activity, and must be stimulated to acquire such function. Conversely, under certain inflammatory conditions, Tregs may undergo rapid reprogramming to acquire helper/effector functions. In this Brief Review, we describe recent progress in elucidating physiologic processes that control the functional status of Foxp3-lineage Tregs. Emerging evidence suggests the surprising possibility that reprogrammed Tregs can be an indispensable source of helper activity in some physiologic settings, such as priming CD8+ T cell responses. This suggests a novel paradigm in which Foxp3+ Tregs intrinsically possess bifunctional potential, acting as a preformed pool of first-responder cells at sites of local inflammation that can either provide classical regulatory/suppressor activity, or rapidly reprogram to supply helper/effector activity, contingent on signals that manifest in local physiologic settings.
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U2 - 10.4049/jimmunol.1002937
DO - 10.4049/jimmunol.1002937
M3 - Review article
C2 - 21464094
AN - SCOPUS:79955008449
SN - 0022-1767
VL - 186
SP - 4535
EP - 4540
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -