Antigen-dependent Proliferation of CD4+ CD25+ Regulatory T Cells In Vivo

By L. Walker, A. Chodos, M. Eggena, H. Dooms, A. Abbas. Journal of Experimental Medicine, 2003

686 citations recorded by the source corpus.

The failure of CD25+ regulatory T cells (Tregs) to proliferate after T cell receptor (TCR) stimulation in vitro has lead to their classification as naturally anergic. Here we use Tregs expressing a transgenic TCR to show that despite anergy in vitro, Tregs proliferate in response to immunization in vivo. Tregs also proliferate and accumulate locally in response to transgenically expressed tissue antigen whereas their CD25− counterparts are depleted at such sites. Collectively, these data suggest that the anergic state that characterizes CD25+ Tregs in vitro may not accurately reflect their responsiveness in vivo. These observations support a model in which Treg population dynamics are shaped by the local antigenic environment.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/3c0103e75cc3141c62a7283d6938e8e1e2f29f4d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Oncology

Citations in the corpus

Developmental Stage, Phenotype, and Migration Distinguish Naive- and Effector/Memory-like CD4+ Regulatory T Cells (2004, background): “Whether the same applies for the adoptively transferred CD25 CD4 T cells, which recently have been reported to undergo excessive in vivo proliferation under particular conditions (31, 32), remains to be shown.”
Control of regulatory T cell lineage commitment and maintenance (2009, background): “Subsequent studies revealed stable expression of high amounts of Foxp3 restricted to Treg cells and its requirement for Treg cell differentiation (Fontenot et al., 2003, 2005c; Hori et al., 2003; Khattri et al., 2003; Wan and Flavell, 2007) and for their suppressor function, proliferative potential,”
An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires (2006, neutral): “(10) AASDYGSSGNKLI (G6) (5) AASEDNNNAPR (B8)”
Natural Recovery and Protection from Autoimmune Encephalomyelitis: Contribution of CD4+CD25+ Regulatory Cells within the Central Nervous System1 (2005, background): “In several models, CD4 CD25 expansion has been found to be localized to the LN draining the target organ or site of immunization (13, 14), so expansion requires a relevant (auto) Ag.”
Mechanisms of foxp3+ T regulatory cell-mediated suppression. (2009, positive): “First, although Treg cells are nonresponsive or anergic to stimulation via the TCR in vitro, Treg cells expand after engagement of their TCR by cognate antigen in a manner indistinguishable from conventional CD4 T cells in vivo (Walker et al., 2003).”
Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells (2004, background): “In addition, Tr1 cells do not appear to be anergic and may efficiently expand in vivo ( 32 ) as they are shown to proliferate by IL-2, IL-4, IL-7, and IL-15 in the present work.”
Dysfunctional Blood and Target Tissue CD4+CD25high Regulatory T Cells in Psoriasis: Mechanism Underlying Unrestrained Pathogenic Effector T Cell Proliferation1 (2005, background): “Because during the immune response the Treg cell population has to expand to perform its suppressor function (1, 50, 51), it is tempting to speculate that the inferior suppressive capacity of psoriatic Treg cells may originate from a defective proliferation and/or activation pathway.”