Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Modigliani, Yves; Thomas‐Vaslin, Véronique; Bandeira, António; Coltey, M; Douarin, Nicole M. Le; Coutinho, António; Salaün, Josselyne

doi:10.1073/pnas.92.16.7555

Cited by 102 publications

(80 citation statements)

References 61 publications

(61 reference statements)

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“…The primary role of regulatory T cells is to inhibit undesirable self-reactive immune responses [1,2]. Regulatory T cells can be divided into subsets on the basis of their development (natural or acquired), cell surface phenotype, secreted proteins and function.…”

Section: Introductionmentioning

confidence: 99%

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

Wang

Davies

2007

International Immunopharmacology

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Treatment with a cocktail of CD4 and CD8-specific monoclonal antibodies (mAb) induces long-term transplantation tolerance and regulatory CD4 + T cells that induce tolerance in non-tolerant T cells. In contrast, treatment with a CD4-specific mAb alone fails to induce long-term tolerance. The current study was designed to test the hypothesis that CD8 blockade plays a role in promoting the development of CD4 + regulatory T cells.Using the DO11.10 CD4 + TCR transgenic mouse model we show that treatment with a CD4/CD8-specific mAb cocktail induces antigen-specific tolerance to OVA, measured by a significant decrease in OVA-specific IgG, on challenge with antigen. Although treatment with OVA and the CD4-specific mAb alone also induces a significant decrease in OVA-specific antibody, the number of DO11.10 cells is significantly greater in mice treated with the CD4/CD8-specific mAb cocktail, and this is associated with a significant increase in proliferation of DO11.10 cells in response to specific antigen. DO11.10 cells sorted from mice made tolerant to OVA with the CD4/CD8-specific mAb cocktail promote an OVA-specific IgG1 (Th2-type) response but not an OVA-specific IgG3 (Th1-type) response on transfer into new syngeneic recipients, suggesting their ability to regulate the type of antigen-specific immune response that ensues after priming with antigen. In addition, DO11.10 cells from tolerant mice express markers that are characteristic of CD4 + regulatory cells, including FOXP3, GITR and CTLA4, but not CD25. Taken as a whole, these data suggest that CD8 blockade promotes CD4 + FOXP3 + regulatory CD4 + T cells by promoting their proliferation in tolerant mice.

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Section: Introductionmentioning

confidence: 99%

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

Wang

Davies

2007

International Immunopharmacology

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“…Regulatory CD4 T cells have been described in a variety of experimental systems to protect from autoimmune diseases (1-6) as well as from inflammatory bowel disease (IBD) 4 (7,8) and allograft rejection (9). Furthermore, regulatory CD4 T cells play a key role in the homeostasis of the peripheral CD4 T cell pool (10).…”

mentioning

confidence: 99%

CD25+ CD4+ T Cells Regulate the Expansion of Peripheral CD4 T Cells Through the Production of IL-10

Annacker

Pimenta-Araujo

Burlen-Defranoux

et al. 2001

The Journal of Immunology

496

395

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The mechanisms by which the immune system achieves constant T cell numbers throughout life, thereby controlling autoaggressive cell expansions, are to date not completely understood. Here, we show that the CD25+ subpopulation of naturally activated (CD45RBlow) CD4 T cells, but not CD25− CD45RBlow CD4 T cells, inhibits the accumulation of cotransferred CD45RBhigh CD4 T cells in lymphocyte-deficient mice. However, both CD25+ and CD25− CD45RBlow CD4 T cell subpopulations contain regulatory cells, since they can prevent naive CD4 T cell-induced wasting disease. In the absence of a correlation between disease and the number of recovered CD4+ cells, we conclude that expansion control and disease prevention are largely independent processes. CD25+ CD45RBlow CD4 T cells from IL-10-deficient mice do not protect from disease. They accumulate to a higher cell number and cannot prevent the expansion of CD45RBhigh CD4 T cells upon transfer compared with their wild-type counterparts. Although CD25+ CD45RBlow CD4 T cells are capable of expanding when transferred in vivo, they reach a homeostatic equilibrium at lower cell numbers than CD25− CD45RBlow or CD45RBhigh CD4 T cells. We conclude that CD25+ CD45RBlow CD4 T cells from nonmanipulated mice control the number of peripheral CD4 T cells through a mechanism involving the production of IL-10 by regulatory T cells.

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“…These Treg cells are classified into naturally occurring Treg cells (3) and those that can be induced by suboptimal antigenic stimulation (4). Naturally occurring CD4 ϩ CD25 ϩ Treg cells are believed to be generated in the thymus, possibly by recognizing self-antigen on epithelial cells (5,6). Such Treg cells have been shown to need for their survival in the periphery the presence of the respective self-antigen (7).…”

mentioning

confidence: 99%

CD8 ⁺ regulatory T cells generated by neonatal recognition of peripheral self-antigen

Reibke

Garbi

Ganss

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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In comparison with CD4 ؉ regulatory T cells, the generation and function of immunomodulatory CD8 ؉ T cells is less well defined. Here we describe the existence of regulatory anti-K b -specific CD8 ؉ T cells that are rendered tolerant during neonatal life via antigen contact exclusively on keratinocytes. These regulatory T cells maintain tolerance during adulthood as they prevent K b -specific graft rejection by naïve CD8 ؉ T cells. Third-party immune responses remain unaffected. Up-regulation of TGF-␤1 and granzyme B in the regulatory CD8 ؉ T cell population suggests the involvement of these molecules in common suppressive pathways shared with CD4 ؉ regulatory T cells. In summary, CD8 ؉ regulatory T cells can be induced extrathymically through antigen contact on neonatally accessible parenchymal cells and maintain tolerance throughout adult life.immune regulation ͉ parenchymal cells ͉ tolerance

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Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Cited by 102 publications

References 61 publications

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

CD25+ CD4+ T Cells Regulate the Expansion of Peripheral CD4 T Cells Through the Production of IL-10

CD8 ⁺ regulatory T cells generated by neonatal recognition of peripheral self-antigen

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Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype.

Cited by 102 publications

References 61 publications

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T cells in vivo

CD25+ CD4+ T Cells Regulate the Expansion of Peripheral CD4 T Cells Through the Production of IL-10

CD8 + regulatory T cells generated by neonatal recognition of peripheral self-antigen

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CD8 ⁺ regulatory T cells generated by neonatal recognition of peripheral self-antigen