T cell tolerance and autoimmunity

Abbas, Abul K.; Lohr, Jens G.; Knoechel, Birgit; Nagabhushanam, Vijaya

doi:10.1016/j.autrev.2004.07.004

Cited by 85 publications

(56 citation statements)

References 14 publications

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“…Peripheral T cell tolerance can be induced and maintained by a variety of mechanisms including deletion, induction of T cell hyporesponsiveness, or differentiation and activation of T regulatory cells (22). The present results demonstrate that resting M are able to suppress allogeneic T cells very efficiently.…”

Section: Discussionsupporting

confidence: 48%

Monocyte-Derived Human Macrophages Mediate Anergy in Allogeneic T Cells and Induce Regulatory T Cells

Hoves

Krause

Schütz

et al. 2006

The Journal of Immunology

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Activation of alloreactive T cells by APCs such as dendritic cells (DC) has been implicated as crucial step in transplant rejection. In contrast, it has been proposed that macrophages (Mφ) maintain tolerance toward alloantigens. It was therefore the aim of this study to further analyze the T cell-stimulatory capacity of mature DC and Mφ in vitro using the model of allogeneic MLR. There was a strong proliferative response in T cells cocultured with DC, which was further increased upon restimulation in a secondary MLR. In contrast, T cells did not proliferate in cocultures with Mφ despite costimulation with anti-CD28 and IL-2. Cytokine analysis revealed considerable levels of IL-10 in cocultures of T cells with Mφ, whereas high amounts of IL-2 and IFN-γ were present in cocultures with DC. There was only minimal T cell proliferation in a secondary MLR when T cells were rescued from primary MLR with Mφ and restimulated with DC of the same donor, or DC of an unrelated donor (third party), whereas a strong primary proliferative response was observed in resting T cells, demonstrating induction of T cell anergy by Mφ. Functional analysis of T cells rescued from cocultures with Mφ demonstrated that anergy was at least partly mediated by IL-10-producing regulatory T cells induced by Mφ. These results demonstrate that Mφ drive the differentiation of regulatory T cells and mediate anergy in allogeneic T cells, supporting the concept that Mφ maintain peripheral tolerance in vivo.

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Section: Discussionsupporting

confidence: 48%

Monocyte-Derived Human Macrophages Mediate Anergy in Allogeneic T Cells and Induce Regulatory T Cells

Hoves

Krause

Schütz

et al. 2006

The Journal of Immunology

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“…Apoptosis of tissue cells preserves organ homeostasis by transducing tolerogenic signals though the dendritic cells and the cross-priming pathway to prevent autoimmunity (25,26). Apoptosis in the immune system promotes peripheral deletion and the removal of dangerous autoreactive T cells (27,28) by using cross-priming to actively silence responsive clones (29). Studies with peptide-induced and superantigen-induced deletion of T cells have helped us understand the mechanisms of peripheral deletion and its importance to the induction of tolerance.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Deletion of Antigen-Specific T Cells Leads to Long-Term Tolerance Mediated by CD8+ Cytotoxic Cells

Herndon

Stuart

Ferguson

2005

The Journal of Immunology

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Peripheral deletion is one mechanism by which potentially self-reactive clones are removed whether they escape thymic deletion. We have examined the consequences of deleting Ag-specific T cells by i.v. injection of soluble Ag. Deletion of DO11.10 T cells by peptide was mediated predominately via a Fas/FasL mechanism. Animals that underwent deletion were tolerant to subsequent immunization with Ag, even when tolerant mice were given fresh Ag-specific DO11.10 T cells before immunization. Tolerance was mediated by CD8+ T cells that killed the DO11.10-transgenic T cells in vivo. These data demonstrate that the programmed cell death of large numbers of T cells leads to peripheral tolerance mediated by CD8+ CTLs.

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“…T cells are important players in normal immunity, but also play a critical role in the development and persistence of autoimmunity [7][8][9]. Clinical studies conducted on IVIgtreated patients have revealed significant modulations of T cell functions in these patients.…”

Section: Introductionmentioning

confidence: 99%

Neutralization of mitogenic lectins by intravenous immunoglobulin (IVIg) prevents T cell activation: does IVIg really have a direct effect on T cells?

Padet

St‐Amour

Aubin

et al. 2011

Clinical and Experimental Immunology

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T cell tolerance and autoimmunity

Cited by 85 publications

References 14 publications

Monocyte-Derived Human Macrophages Mediate Anergy in Allogeneic T Cells and Induce Regulatory T Cells

Monocyte-Derived Human Macrophages Mediate Anergy in Allogeneic T Cells and Induce Regulatory T Cells

Peripheral Deletion of Antigen-Specific T Cells Leads to Long-Term Tolerance Mediated by CD8+ Cytotoxic Cells

Neutralization of mitogenic lectins by intravenous immunoglobulin (IVIg) prevents T cell activation: does IVIg really have a direct effect on T cells?

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