CD28 co-stimulatory regimes differ in their dependence on phosphatidylinositol 3-kinase: common co-signals induced by CD80 and CD86

Céfaï, Daniel; Cai, Yun-Cai; Hu, Hui; Rudd, Christopher E.

doi:10.1093/intimm/8.10.1609

Cited by 26 publications

(14 citation statements)

References 17 publications

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“…The blot was stripped and reprobed with anti-CBL to verify equivalent protein levels (bottom). The data reported here and other studies (21,22) have shown that both CD80 and CD86 are able to induce the association of PI3-K with CD28 and that this association is dependent upon the phosphorylated YMNM motif of the CD28 cytoplasmic domain. Our conclusions differ, however, from those of Rudd and colleagues (22) who reported no difference in the ability of CD80 and CD86 to induce the SH2-dependent association of PI3-K and CD28.…”

Section: Stimulation With Cd80 or Cd86 Induces The In Vivo Tyrosine Psupporting

confidence: 80%

“…The data reported here and other studies (21,22) have shown that both CD80 and CD86 are able to induce the association of PI3-K with CD28 and that this association is dependent upon the phosphorylated YMNM motif of the CD28 cytoplasmic domain. Our conclusions differ, however, from those of Rudd and colleagues (22) who reported no difference in the ability of CD80 and CD86 to induce the SH2-dependent association of PI3-K and CD28. These investigators studied a murine CD28 ϩ hybridoma transfected with human CD28 that was stimulated with plate-bound CHO cells expressing murine CD80 and CD86 proteins; both CD80 and CD86 induced the association of PI3-K with CD28.…”

Section: Stimulation With Cd80 or Cd86 Induces The In Vivo Tyrosine Psupporting

confidence: 80%

See 1 more Smart Citation

CD80 and CD86 Are Not Equivalent in Their Ability to Induce the Tyrosine Phosphorylation of CD28

Slavik

Hutchcroft

Bierer

1999

Journal of Biological Chemistry

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Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation. We have examined early signal transduction pathways recruited following T cell stimulation with either CD80 or CD86. Purified human peripheral T cells or Jurkat T cells were stimulated with Chinese hamster ovary (CHO) cells expressing either human CD80 (CHO-CD80) or human CD86 (CHO-CD86) or with anti-CD28 monoclonal antibody (mAb). In the presence of phorbol 12-myristate 13-acetate, both CHO-CD80 and CHO-CD86, like anti-CD28 mAb, were capable of stimulating cytokine production from both human peripheral T cells and Jurkat T cells. Both CHO-CD80 and CHO-CD86, in the presence of anti-CD3 mAb, costimulated NFAT-dependent transcriptional activation. Several intracellular signaling proteins, such as CBL and VAV, were phosphorylated on tyrosine in response to CD80, CD86, and anti-CD28 mAb. Surprisingly, although stimulation of Jurkat T cells with either CHO-CD80 or anti-CD28 mAb resulted in robust tyrosine phosphorylation of CD28 itself, ligation with CHO-CD86 was unable to induce detectable CD28 tyrosyl phosphorylation over a range of stimulation conditions. In addition, the association of phosphoinositide 3-kinase with CD28 and enhanced tyrosine phosphorylation of phospholipase C␥ were seen after anti-CD28 mAb and CHO-CD80 stimulation but to a much lesser extent after CHO-CD86 stimulation. Thus, ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT-mediated transcriptional activation, and to the costimulation of interleukin-2 and granulocyte-macrophage colonystimulating factor production. However, CD80 and CD86 also induce distinct signal transduction pathways including the tyrosine phosphorylation of CD28 and phospholipase C␥1 and the SH2-dependent association of phosphoinositide 3-kinase with CD28. These quantitative, if not qualitative, differences between signaling initiated by these two ligands for CD28 may contribute to functional differences (e.g. Th1 or Th2 differentiation) in T cell responses.Activation and maturation of resting T lymphocytes can be achieved by antigen-specific interactions of the TcR-CD3 complex in concert with a second, antigen-nonspecific signal. This second, costimulatory signal has been shown to prevent the induction of T cell anergy and to enhance cytokine production, notably IL-2 1 (1-3). Found on more than 95% of human CD4 ϩ T cells and on about 50% of human CD8 ϩ T cells, the cellsurface molecule CD28 is a major T cell costimulatory receptor. Engagement of the CD28 receptor with anti-CD28 mAb or by ligand prevents the induction of T cell anergy and supports IL-2 production and T cell proliferation.The B7 family members CD80 (B7-1) and CD86 (B7-2) are two principal ligands for CD28 and for CTLA-4 (CD152), a second CD28 family member. Whereas only 25% homologous by amino acid sequence, CD80 and CD86 bind CD28 with similar low affinities ...

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Section: Stimulation With Cd80 or Cd86 Induces The In Vivo Tyrosine Psupporting

confidence: 80%

Section: Stimulation With Cd80 or Cd86 Induces The In Vivo Tyrosine Psupporting

confidence: 80%

CD80 and CD86 Are Not Equivalent in Their Ability to Induce the Tyrosine Phosphorylation of CD28

Slavik

Hutchcroft

Bierer

1999

Journal of Biological Chemistry

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“…A recent report has suggested that Vav-1 has no apparent role in co-stimulation based on the evidence that Vav-1-deficient T cells activated by anti-CD28 Ab and PMA showed no defect in proliferation and IL-2 production (55). This type of stimulation which generates CsA-resistant lymphokine expression (56), is likely to be supraphysiological and to bypass relevant signaling steps elicited by cell surface receptors (57). Indeed, CD28 enhancement of a TCR-induced increase in IL-2 mRNA is potently, though not entirely, inhibited by CsA (56, 58) and we found that NF-AT activation induced by Vav-1 overexpression/CD28 engagement (Fig.…”

Section: Discussionmentioning

confidence: 68%

CD28 Utilizes Vav-1 to Enhance TCR-Proximal Signaling and NF-AT Activation

Michel

Mangino

Attal-Bonnefoy

et al. 2000

The Journal of Immunology

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The mechanism through which CD28 costimulation potentiates TCR-driven gene expression is still not clearly defined. Vav-1, an exchange factor for Rho GTPases thought to regulate, mainly through Rac-1, various signaling components leading to cytokine gene expression, is tyrosine phosphorylated upon CD28 engagement. Here, we provide evidence for a key role of Vav-1 in CD28-mediated signaling. Overexpression of Vav-1 in Jurkat cells in combination with CD28 ligation strongly reduced the concentration of staphylococcus enterotoxin E/MHC required for TCR-induced NF-AT activation. Surprisingly, upon Vav-1 overexpression CD28 ligation sufficed to activate NF-AT in the absence of TCR engagement. This effect was not mediated by overexpression of ZAP-70 nor of SLP-76 but necessitated the intracellular tail of CD28, the intactness of the TCR-proximal signaling cascade, the Src-homology domain 2 (SH2) domain of Vav-1, and SLP-76 phosphorylation, an event which was favored by Vav-1 itself. Cells overexpressing Vav-1 formed lamellipodia and microspikes reminiscent of Rac-1 and Cdc42 activation, respectively, for which the SH2 domain of Vav-1 was dispensable. Together, these data suggest that CD28 engagement activates Vav-1 to boost TCR signals through a synergistic cooperation between Vav-1 and SLP-76 and probably via cortical actin changes to facilitate the organization of a signaling zone.

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“…It participates in various regulating mechanisms, for example in cytoplasmic-to nuclear signaling, vesicle transport, cytoskeletal rearrangements and CD28-B7 outside-inside signaling [1,4,5]. Important target molecules are the small Rho GTPases, which are involved in cytoskeletal organization.…”

Section: Introductionmentioning

confidence: 99%