The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells.

Koulova, Lydia; Clark, Edward A.; Shu, Geraldine; Dupont, Bo

doi:10.1084/jem.173.3.759

Cited by 306 publications

(152 citation statements)

References 11 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…B7.1 (CD80), one of the first identified members of the B7 family, binds to CD28 to transmit stimulatory signaling and thus enhances activation of T lymphocytes. [43][44][45][46] Decades ago, researchers introduced the CD80 gene into mouse tumor cells to achieve tumor rejection, which was predominantly dependent on NK and CD8 C T cells but not on CD4 C T cells, 47,48 suggesting an innate-like immune response pattern. In the first clinical trial using a recombinant CD80 vaccinia virus to treat accessible melanoma lesions, 3 of 12 patients had partial responses and stable disease.…”

Section: Discussionmentioning

confidence: 99%

Regulation of NKG2D⁺CD8⁺T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Batth

Xia

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

The natural killer (NK) group 2D (NKG2D) receptor, which displays on mouse and human NK cells, activates CD8 C T cells and small subsets of other T cells. NKG2D C CD8 C T cells play critical roles in both innate and adaptive immunity upon engagement with NKG2D ligands to eliminate tumor and infected cells. Despite the important role of NKG2D C CD8 C T cells in immune surveillance, the mechanisms of how NKG2D expression on CD8 C T cells is regulated remain poorly defined. We treated mouse and human CD8 C T cells with CD80 recombinant protein, plus a pharmacologic model with small molecular inhibitors to determine which signaling pathway leads to NKG2D regulation on CD8 C T cells. This study revealed that CD28 activation gives rise to sustained NKG2D expression on both mouse and human CD8 C T cells in a signal transducer and activator of transcription 3 (STAT3) phosphorylation-dependent manner. Further, we found that CD28 activation stimulated sustained activation of the tyrosine kinase Lck, which recruits and triggers Janus kinase/STAT3 signaling to phosphorylate STAT3, and in turn increases NKG2D expression. Moreover, NKG2D induction on CD8 C T cells exerts cytolytic activity against target tumor cells in vitro, as well as significantly improves the antitumor therapeutic effects in vivo in an NKG2D-dependent manner. Taken together, these results elucidated a novel mechanism of NKG2D regulation by phosphorylated STAT3 (pSTAT3) on CD8 C T cells upon CD28 activation. This mechanism may shed light on the effectiveness of CD80-based, NKG2D-dependent antitumor immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of NKG2D⁺CD8⁺T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Batth

Xia

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

show abstract

“…In addition, full activation of these cells requires the binding of costimulatory molecules expressed on one cell to costimulatory molecules expressed on the other (3,4). One such costimulatory molecule is CD86 (B7-2), which is expressed at a low level on a resting B cell (5,6), but is up-regulated following the stimulation of BCR (7,8), CD40 (9,10), MHC class II (11), LPS receptor (5,7,12,13), IL-4R (14,15), and/or ␤ 2 -adrenergic receptor (␤ 2 AR) (16,17). CD86 binds to the costimulatory molecule CD28 on the Th cell to increase the expression of the costimulatory molecule CD40 ligand (CD40L) on the Th cell and also to increase the level of cytokine produced by the Th cell (13,15,18).…”

Section: Selective Regulation Of Mature Igg1 Transcription By Cd86mentioning

confidence: 99%

Selective Regulation of Mature IgG1 Transcription by CD86 and β2-Adrenergic Receptor Stimulation

Podojil

Sanders

2003

The Journal of Immunology

View full text Add to dashboard Cite

Stimulation of CD86 and the β2-adrenergic receptor (β2AR) on a B cell, either alone or together, is known to increase the level of IgG1 protein produced by a CD40 ligand/IL-4-activated B cell. It is also known that the mechanism by which CD40 and IL-4R stimulation on a B cell increases the level of IgG1 protein is by increasing germline γ1 transcription, IgG1 class switching, and mature IgG1 transcription, while the molecular mechanism responsible for mediating the CD86- and β2AR-induced effect remains unknown. In the present study using real-time PCR we show that the level of mature IgG1 transcription increases in CD40 ligand/IL-4-activated B cells following stimulation of either CD86 and/or β2AR, and that this increase reflects the increase in IgG1 protein. Furthermore, we show that the CD86- and/or β2AR-induced increase in mature IgG1 transcript is due to an increase in the rate of mature IgG1 transcription, as determined by nuclear run-on analysis. This effect is additive when both receptors are stimulated and is lost when B cells from CD86- and β2AR-deficient mice are used. In contrast, the level of germline γ1 transcription, the stability of mature IgG1 transcript, the number of IgG1-positive B cells, and the number of IgG1-secreting B cells did not change. These results provide the first evidence that CD86 and/or β2AR stimulation on a CD40 ligand/IL-4-activated B cell increases the level of IgG1 protein produced per cell by increasing the rate of mature IgG1 transcription.

show abstract

“…Since more is known about CD28, it is easiest to speculate on its potential role. For example, initial contact between a T and a B cell bearing the relevant antigen would result not only in augmented T cell adhesion due to CD3/TCR engagement, but also in induction of B cell B7 expression due to the engagement of MHC class II (32). Subsequent interaction between T cell CD28 and B cell B7 would result in activation via CD28 and longer cell-cell contact, ultimately resulting in functional responses such as cytokine production, proliferation, and differentiation.…”

Section: Regulation Of Differential Naive and Memory T Cell Adhesion mentioning

confidence: 99%

“…Alternatively, it is possible that CD7 and CD28 may sometimes modulate adhesion independently of CD3 engagement or preceding that engagement. This would require the ligand to be expressed on the apposing cell prior to T cell contact, as would occur with previously activated B cells, activated monocytes, or certain thymic stromal cells (32)(33)(34). Progress in understanding CD7 will depend on definition of its natural ligands.…”

Section: Regulation Of Differential Naive and Memory T Cell Adhesion mentioning

confidence: 99%

Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.

Shimizu

Seventer

Ennis

et al. 1992

The Journal of Experimental Medicine

176

View full text Add to dashboard Cite

SummaryRegulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca 2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression."[ mphocytes express a multitude of cell surface receptors .1_r that are capable of mediating adhesion to other cells and proteins (1, 2). Regulation of the functional activity of these adhesion molecules is critical to both T cell migration and recognition, since T cells must transiently interact with cells and proteins found in the extracellular environment. One important element in the regulation of adhesion is the rapid increase in the adhesive function of integrin molecules that occurs after crosslinking of the CD3/TCR complex by mAb (3-6) or foreign antigen (7). Integrins mediate T cell adhesion to other cells via interactions such as LFA-1 binding to its ligands ICAM-1 and ICAM-2, and VLA-4 binding to VCAM-1, and also to extraceUular matrix (ECM) 1 components via interactions such as VLA-4 and VLA-5 to fibronectin (FN) (1, 2, 8). Activation of other lymphoid cell types by mAb crosslinking of functionally relevant cell surface molecules also results in increased LFA-l-dependent adhesion. Such molecules include HLA class II (9) and CD14 (10) on monocytes, and surface immunoglobulin (11), CD19 (12), and CD40 (13) We reasoned that the functional activity of integrin molecules on human T cells might also be increased by mAb crosslinking of other molecules besides the CD3/TCR. In this study we report the ability of three different activation signals to increase integrin-mediated adhesion: the Ca 2 + ionophore A23187, and mAb crosslinking of the CD7 and CD28 molecules, both of which have been implicated as T cell activation molecules (14-16). These activation signals can coordinately increase T cell adhesion to three different ligands: the LFA-1 ligand ICAM-1, the VLA-4 endothelial cell surface ligand VCAM-1, and the VLA-4 and VLA-5 ligand FN. We demonstrate similarities in the biochemical signals generated by CD3, CDT, and CD28 crosslinking that distinguish receptor-mediated activation from the eff...

show abstract

The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells.

Cited by 306 publications

References 11 publications

Regulation of NKG2D⁺CD8⁺T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Regulation of NKG2D⁺CD8⁺T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Selective Regulation of Mature IgG1 Transcription by CD86 and β2-Adrenergic Receptor Stimulation

Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.

Contact Info

Product

Resources

About

The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells.

Cited by 306 publications

References 11 publications

Regulation of NKG2D+CD8+T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Regulation of NKG2D+CD8+T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Selective Regulation of Mature IgG1 Transcription by CD86 and β2-Adrenergic Receptor Stimulation

Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.

Contact Info

Product

Resources

About

Regulation of NKG2D⁺CD8⁺T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism

Regulation of NKG2D⁺CD8⁺T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism