EFIS Lecture: Understanding the CTLA-4 checkpoint in the maintenance of immune homeostasis

Walker, Lucy S. K.

doi:10.1016/j.imlet.2017.02.007

Cited by 52 publications

(46 citation statements)

References 98 publications

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“…Importantly, we found that recruitment of Tfr cells into GC was independent of the immunizing antigen. 53,[110][111][112] Indeed, mice selectively lacking CTLA-4 expression on Treg cells succumbed to spontaneous lymphoproliferation with fatal T-cell-dependent autoimmune disease. 98 The lack of specificity of Tfr [104][105][106][107][108] Curiously, a recent report found that adenosine A2a receptor agonists can limit GC and Tfh cell responses following immunization, suggesting adenosine may indeed be a key mediator of Tfr-cell effector functions in humoral responses.…”

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

“…109 CTLA-4 has a widely known function in maintaining immune homeostasis and in mediating Treg cell function. 111,112,114 As CTLA-4 on Tfr cells has an expression comparable to activated highly suppressive Treg cells, two independent groups extensively studied the role of CTLA-4 in Tfr-cell function. 53,113 Briefly, CTLA-4 works in a cell-extrinsic manner by capturing ligands from the surface of APCs, thereby limiting CD28 engagement.…”

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

“…109 CTLA-4 has a widely known function in maintaining immune homeostasis and in mediating Treg cell function. 53,[110][111][112] Indeed, mice selectively lacking CTLA-4 expression on Treg cells succumbed to spontaneous lymphoproliferation with fatal T-cell-dependent autoimmune disease. 53,113 Briefly, CTLA-4 works in a cell-extrinsic manner by capturing ligands from the surface of APCs, thereby limiting CD28 engagement.…”

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

“…114 In a highly endocytic behavior, CTLA-4 can strip APCs of costimulatory ligands (CD80 and CD86), directing those ligands to lysosomes for degradation, and then being recycled back to the cell surface to repeat the process. 111,112,114 As CTLA-4…”

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

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T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr‐cell compartments

Fonseca

Ribeiro

Graça

2019

Immunological Reviews

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Summary Germinal centers (GC) have been known as key anatomic structures in humoral immunity, where isotype switching and affinity maturation occur. As a consequence, elucidation of GC regulation has potential implications for the understanding of autoantibody‐mediated diseases. It is now accepted that different regulatory mechanisms coexist, including the action of a specialized population of Foxp3+ regulatory T cells with unique access to the B‐cell follicle: the T follicular regulatory (Tfr) cells. Tfr cells develop through a multistep process requiring migration through different compartments of lymphoid tissues. This review discusses the ontogeny and physiology of Tfr cells, their distribution within distinct anatomic compartments, and their function. A greater understanding of Tfr biology and GC regulation is likely to lead to better stratification of patients with autoantibody‐mediated diseases, and to the identification of novel therapeutic targets.

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Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

Section: Tfr-cell Antigen Specificitymentioning

confidence: 99%

See 2 more Smart Citations

T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr‐cell compartments

Fonseca

Ribeiro

Graça

2019

Immunological Reviews

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“…The coinhibitory cytotoxic T-lymphocyte associated protein 4 (CTLA-4), which is expressed on activated T cells also binds to CD80 or CD86 and interrupts T cell activation (15,16). After TCR ligation by specific antigens, T cells are stimulated to proliferate and differentiate into the cytotoxic effectors Th1 and Th2 helper cells, regulatory T cells, Th17 cells, or follicular helper T cells, which are influenced by the cytokine milieu and strength and duration of the TCR signal (17,18).…”

Section: Tcr Signaling and Its Regulatory Factorsmentioning

confidence: 99%

Aplastic anemia is related to alterations in T cell receptor signaling

Xiao¹,

Zhao²,

Li³

2017

Stem Cell Investig.

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Aplastic anemia (AA) is a disease characterized by bone marrow hematopoietic dysfunction and peripheral blood pancytopenia, which is thought to be mediated by an abnormal T cell-induced immune response. T cell receptor (TCR) signaling is pivotal for T cell development and function. An aberrant TCR signaling leads to an unbalanced immune system that can result in a range of immune-related disorders, including autoimmune diseases, chronic infections, and tumors. In this article, we briefly review the T cell immune pathophysiology of AA, the physiology of normal TCR signaling and its regulatory factors, and clinical and laboratory findings of TCR signaling molecules and their regulatory factors in AA.

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Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

Zhang

Sun

2020

Eur J Immunol

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Regulatory T (Treg) cells are a specialized subpopulation of T cells that plays critical roles in the maintenance of immune homeostasis. Although efforts have been done, their role in human pregnancy is not fully understood. Numerous studies reported the presence of Treg cells throughout gestation by promoting maternal-fetal tolerance and fetal development. Furthermore, Treg population is heterogeneous as it is expressing different immune checkpoint molecules favoring immune suppressive function. Therefore, better understanding of the heterogeneity and function of Treg cells during pregnancy is critical for an effective immune intervention. Latest evidence has shown that several immune checkpoint molecules are closely associated with pregnancy outcome via multiple inhibitory mechanisms. Majority of these studies demonstrated the modulatory effects of immune checkpoint molecules on effector T-cell immunity, but their effects onTreg activation and function are still an enigma. In this review, we emphasize the potential influence of multiple immune checkpoint molecules, including CTLA-4, PD-1, Tim-3, LAG-3, and TIGIT, either in membrane or soluble form, on the function of decidual and peripheral Treg cells during pregnancy. Additionally, we discuss the promising future of targeting Treg cells via immune checkpoint molecules for pregnancy maintenance and prevention of complicated pregnancies.Keywords: CTLA-4 r PD-1 r pregnancy r Tim-3 r Treg cells

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EFIS Lecture: Understanding the CTLA-4 checkpoint in the maintenance of immune homeostasis

Cited by 52 publications

References 98 publications

T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr‐cell compartments

T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr‐cell compartments

Aplastic anemia is related to alterations in T cell receptor signaling

Immune checkpoint molecules in pregnancy: Focus on regulatory T cells

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