Regulatory T cells: Development, function and role in autoimmunity

Lan, Ruth Y.; Ansari, Aftab A.; Lian, Zhe Xiong; Gershwin, M. Eric

doi:10.1016/j.autrev.2005.01.007

Cited by 189 publications

(162 citation statements)

References 40 publications

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“…Elimination of C3, as well as CD55, in the double-knockout mice restored normal levels of IFN-␥ but not of IL-10, indicating that IL-10 down-regulation is not related to an increase in complement activation but might be related to CD55 downstream signaling. Among T lymphocytes, IL-10 is produced by the T regulatory cells, both the naturally occurring thymic CD4 ϩ CD25 ϩ or those generated in the periphery, the adaptive regulatory T cells such as T-reg 1 and Th3 (33,34). In CD55-deficient mice, IL-10 reduction did not correlate with differences in thymic regulatory cells (19).…”

Section: Discussionmentioning

confidence: 98%

Costimulation via CD55 on Human CD4+ T Cells Mediated by CD97

Capasso

Durrant

Stacey

et al. 2006

The Journal of Immunology

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Decay-accelerating factor (CD55) is a complement regulatory protein, which is expressed by most cells to protect them from complement-mediated attack. CD55 also binds CD97, an EGF-TM7 receptor constitutively expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells upon activation. Early results suggested that CD55 could further enhance T cell proliferation induced by phorbol ester treatment. The present study demonstrates that coengagement of CD55, using either cross-linking mAbs or its natural ligand CD97, and CD3 results in enhanced proliferation of human peripheral blood CD4+ T cells, expression of the activation markers CD69 and CD25, and secretion of IL-10 and GM-CSF. Recently, an increase in T cell responsiveness in CD55−/− mice was shown to be mediated by a lack of complement regulation. In this study, we show that direct stimulation of CD55 on CD4+ T cells with CD97 can modulate T cell activation but does not interfere with CD55-mediated complement regulation. Our results support a multifaceted role for CD55 in human T cell activation, constituting a further link between innate and adaptive immunity.

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Section: Discussionmentioning

confidence: 98%

Costimulation via CD55 on Human CD4+ T Cells Mediated by CD97

Capasso

Durrant

Stacey

et al. 2006

The Journal of Immunology

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“…It has recently been recognized that CD4 + CD25 + Treg cells play an important role in the negative regulation of immune responses and the prevention of autoimmunity (11)(12)(13). These cells are non-responsive (anergic) to TCR stimulation and can suppress proliferation of CD4 + CD25 -T target cells in culture.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, mutations affecting FOXP3, a transcription factor required for the development of this lineage, lead to severe autoimmune disorders in humans and mice (14)(15)(16)(17)(18)(19). Abnormal Treg function has also been demonstrated in several human autoimmune disorders, including type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis (12). We therefore hypothesized that abnormalities in Treg cells may contribute to the pathogenesis of autoimmune complications associated with WAS.…”

Section: Introductionmentioning

confidence: 99%

Impaired in vitro regulatory T cell function associated with Wiskott–Aldrich syndrome

Adriani

Aoki

Horai

et al. 2007

Clinical Immunology

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Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency characterized by the contradictory coexistence of impaired T-cell function and exaggerated T-cell-mediated pathology, including autoimmunity and eczema. WAS protein (WASp)-deficient mice are also immunodeficient and can develop autoimmune disease. Since defects in regulatory T-cells (Treg) are associated with autoimmunity, we examined the presence and function of these cells in WAS patients and WASpdeficient mice. We found that CD4 + CD25 + FOXP3 + Treg cells can develop in the absence of WASp expression. However, Treg cells both from WASp-deficient mice and from four out of five WAS patients studied showed impaired in vitro suppressor function. In WASp-deficient mice, this defect could be partially rescued by pre-activation with IL-2, suggesting that inadequate cell activation may play a role in WASp-deficient Treg dysfunction. These findings may provide insights into the complex pathophysiology and paradoxical phenotypes of WAS and suggest new therapeutic modalities for autoimmunity in these patients.

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“…18 Tregs have been found to play a role in a number of human autoimmune diseases. [19][20][21][22][23] Most studies, however, have been performed primarily with peripheral blood samples. Direct cell-to-cell contact generally appeared to be a requirement by which Tregs mediate their regulatory function.…”

mentioning

confidence: 99%