Article

Regulatory T-cell compartmentalization and trafficking

Department of Surgery, University of Michigan, Ann Arbor, USA.
Blood (Impact Factor: 9.78). 08/2006; 108(2):426-31. DOI: 10.1182/blood-2006-01-0177
Source: PubMed

ABSTRACT CD4(+)CD25(+)FOXP3(+) regulatory T cells (CD4(+) Treg cells) are thought to differentiate in the thymus and immigrate from the thymus to the periphery. Treg cells can regulate both acquired and innate immunity through multiple modes of suppression. The cross-talk between Treg cells and targeted cells, such as antigen-presenting cells (APCs) and T cells, is crucial for ensuring suppression by Treg cells in the appropriate microenvironment. Emerging evidence suggests that Treg compartmentalization and trafficking may be tissue or/and organ specific and that distinct chemokine receptor and integrin expression may contribute to selective retention and trafficking of Treg cells at sites where regulation is required. In this review, the cellular and molecular signals that control specialized migration and retention of Treg cells are discussed.

0 Followers
 · 
93 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are in widespread use due to their LDL reducing properties and concomitant improvement of clinical outcome in patients with and without preexisting atherosclerosis. Considerable evidence suggests that immune mediated mechanisms play a dominant role in the beneficial effects of statins. Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) have a key role in the prevention of various inflammatory and autoimmune disorders by suppressing immune responses. We tested the hypothesis that statins influence the circulating number and the functional properties of Tregs. We studied the effects of in vivo and in vitro statin treatment of human and murine mononuclear cells on the number of Tregs and the expression level of their master transcription regulator, Foxp3. Atorvastatin, but not mevastatin nor pravastatin, treatment of human peripheral blood mononuclear cells (PBMCs) increased the number of CD4(+)CD25(high) cells, and CD4(+)CD25(+)Foxp3(+) cells. These Tregs, induced by atorvastatin, expressed high levels of Foxp3, which correlated with an increased regulatory potential. Furthermore, co-culture studies revealed that atorvastatin induced CD4(+)CD25(+)Foxp3(+) Tregs were derived from peripheral CD4(+)CD25(-)Foxp3(-) cells. Simvastatin and pravastatin treatment in hyperlipidemic subjects increased the number of Tregs. In C57BL/6 mice however, no effect of statins on Tregs was evident. In conclusion, statins appear to significantly influence the peripheral pool of Tregs in humans. This finding may shed light on the mechanisms governing the plaque stabilizing properties of statins.
    Atherosclerosis 05/2008; 197(2):829-39. DOI:10.1016/j.atherosclerosis.2007.07.031 · 3.97 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To establish a characterized model of regulatory T cell (Treg) depletion in the cat we assessed the kinetics of depletion and rebound in peripheral and central lymphoid compartments after treatment with anti-CD25 antibody as determined by cell surface markers and FOXP3 mRNA expression. An 82% decrease in circulating CD4+CD25+ Tregs was observed by day 11 after treatment. CD4+CD25+ cells were also reduced in the thymus (69%), secondary lymphoid tissues (66%), and gut (67%). Although CD4+CD25+ cells rebound by day 35 post-treatment, FOXP3 levels remain depressed suggesting anti-CD25 antibody treatment has a sustainable diminutive effect on the Treg population. To determine whether CD25+ Treg depletion strategies also deplete activated CD25+ effector cells, cats were immunized with feline immunodeficiency virus (FIV) p24-GST recombinant protein, allowing them to develop a measurable memory response, prior to depletion with anti-CD25 antibody. Anti-FIV p24-GST effector cell activity in peripheral blood after depletion was sustained as determined by antigen-specific T cell proliferation and humoral responses against FIV p24-GST with an ELISA for antigen-specific feline IgG. Furthermore, development of an anti-mouse response in Treg-depleted cats was similar to control levels indicating the retained capacity to respond to a novel antigen. We conclude that despite alterations in CD25+ cell levels during depletion, the feline immune system remains functional. We demonstrate here a model for the study of disease pathogenesis in the context of reduced numbers of immunosuppressive CD4+CD25+ Tregs throughout the feline immune system.
    Journal of Immunological Methods 02/2008; 329(1-2):81-91. DOI:10.1016/j.jim.2007.09.015 · 2.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is well established that CD8 + cytotoxic T lymphocytes (CTLs) play a major role in eradicating tumor cells. The path from naive CD8 + T cell to effector CD8 + T cell is guided by antigen presenting cells, such as dendritic cells (DCs) that start a developmental program in the CD8 + T cells through the delivery of MHC/peptide complexes, co-stimulatory and pro-inflammatory signals. These signals determine the magnitude of the ensuing response and the ability of the CD8 + CTLs to successfully complete their quest, eradicating tumor cells whilst conquering enemies, such as immunosuppressive regulatory T cells (Tregs). In this chapter, we discuss the role of DCs and of the signals critical for effector CD8 + T cell differentiation, and how the differences in the nature of these signals contribute to the diversity of CD8 + T cell responses. No part of this digital document may be reproduced, stored in a retrieval system or transmitted commercially in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services.
    Horizons in Cancer Research, Edited by Hiroto S. Watanabe, 01/2013: chapter Priming of Cytotoxic T Lymphocyte Responses by Dendritic Cells: Induction of Potent Anti-tumor Immune Responses; Nova Science Publishers., ISBN: 978-1-62417-328-8

Preview