CD28 as a Molecular Amplifier Extending TCR Ligation and Signaling Capabilities

Michel, Frédérique; Attal-Bonnefoy, Géraldine; Mangino, Giorgio; Mise-Omata, Setsuko; Acuto, Oreste

doi:10.1016/s1074-7613(01)00244-8

Cited by 165 publications

(165 citation statements)

References 58 publications

(1 reference statement)

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“…It has been reported that the stimulation of CD3 increases [Ca 2+ ] i via the activation of PLC-γ and that the level is further increased by the addition of CD28.6 under slightly alkaline conditions [29,30]. Our present data confirmed the previous results at pH 7.6 ( Figure 3).…”

Section: + ] I Under Acidic Conditionssupporting

confidence: 92%

TCR Signaling via ZAP-70 Induced by CD3 Stimulation is More Active Under Acidic Conditions

Hatatani¹

2013

J Cell Sci Ther

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Section: + ] I Under Acidic Conditionssupporting

confidence: 92%

TCR Signaling via ZAP-70 Induced by CD3 Stimulation is More Active Under Acidic Conditions

Hatatani¹

2013

J Cell Sci Ther

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“…This synergistic signal could differentially activate multiple transcription factors such as NFkB, NFAT and activator protein-1 (AP1). 100 Further work is still needed to establish more clearly the full range of functions controlled by the unique array of mediators coupled to CD28.…”

Section: Discussionmentioning

confidence: 99%

“…99 This pathway may work in conjunction with CD28-GRb2 and Vav1 where Vav1 GEF activity is needed for PKC-u translocation to the membrane. [99][100][101] …”

Section: Cd28-ymnm and Grb2mentioning

confidence: 99%

CD28 co‐signaling in the adaptive immune response

Riha¹,

Rudd²

2010

Self/Nonself

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“…As an integral component of the immunological synapse, CD28 plays a critical role in the recruitment of signaling molecules to the TCR (2). In particular, it has been recently demonstrated that CD28 enhances close contact between T cells and antigen-presenting cells and facilitates TCR signal transduction by amplifying phospholipase C␥1 activation and Ca 2ϩ response (3). The consequence of this action is an augmentation of early TCR-mediated signal (4).…”

mentioning

confidence: 99%

CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-κB subunits onIL-8andBcl-xLgene promoters

Marinari

Costanzo

Marzano

et al. 2004

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

108

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CD28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. The CD28 receptor can enhance T cell antigen receptor (TCR) signals, as well as deliver independent signals. Indeed, CD28 engagement by B7 can generate TCR-independent signals leading to I B kinase and NF-B activation. Here we demonstrate that the TCR-independent CD28 signal leads to the selective transcription of survival (Bcl-xL) and inflammatory (IL-8 and B cell activation factor, but not proliferative (IL-2), genes, in a NF-Bdependent manner. CD28-stimulated T cells actively secrete IL-8, and Bcl-xL up-regulation protects T cells from radiation-induced apoptosis. The transcription of CD28-induced genes is mediated by the specific recruitment of RelA and p52 NF-B subunits to target promoters. In contrast, p50 and c-Rel, which preferentially bind NF-B sites on the IL-2 gene promoter after anti-CD3 stimulation, are not involved. Thus, we identify CD28 as a key regulator of genes important for both survival and inflammation. C D28 is one of the most important costimulatory receptors necessary for full T lymphocyte activation. Early studies on CD28 demonstrated that it provides a potent signal for the upregulation of several cytokines, acting at the level of both transcription and message stability. More recent studies have evidenced that CD28 plays a key role in enhancing T cell activation by the T cell antigen receptor (TCR) (1). As an integral component of the immunological synapse, CD28 plays a critical role in the recruitment of signaling molecules to the TCR (2). In particular, it has been recently demonstrated that CD28 enhances close contact between T cells and antigen-presenting cells and facilitates TCR signal transduction by amplifying phospholipase C␥1 activation and Ca 2ϩ response (3). The consequence of this action is an augmentation of early TCR-mediated signal (4). Recent evidence showing that CD28 can mediate adhesion signals beyond costimulatory ones (3) has led to new interest and induced a new wave of investigation of the intriguing problems concerning the molecular mechanisms as well as the targets of CD28 as an independent signaling unit. CD28 stimulation can induce cytoskeletal rearrangements in T cells (5) or up-regulate IL-2-4 only when Vav and the adapter SLP-76 are overexpressed (6). However, the mediators and the molecular mechanisms, which govern the process whereby CD28 may deliver an autonomous signal, remain unknown. We have recently demonstrated that CD28 engagement by B7 can generate TCRindependent signals leading to I B kinase (IKK) and NF-B activation (7) and that Vav-1 acts as the upstream regulator of this signaling pathway (8).NF-B͞Rel transcription factors are critical regulators of the positioning of immune responses to integrate information from both innate and adaptive immune signaling pathways. In mammals, this family consists of five members that form homo-and heterodimeric complexes including NF-B1 (p50 and its precursor p105), NF-B2 (p52 and its precursor p100), RelA...

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CD28 as a Molecular Amplifier Extending TCR Ligation and Signaling Capabilities

Cited by 165 publications

References 58 publications

TCR Signaling via ZAP-70 Induced by CD3 Stimulation is More Active Under Acidic Conditions

TCR Signaling via ZAP-70 Induced by CD3 Stimulation is More Active Under Acidic Conditions

CD28 co‐signaling in the adaptive immune response

CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-κB subunits onIL-8andBcl-xLgene promoters

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