Signalling through CD28 T-cell activation pathway involves an inositol phospholipid-specific phospholipase C activity

Nunès, Jacques A.; Klasen, Sandrine; Franco, Marie-Dominique; Lipcey, Carol; Mawas, Claude; Bagnasco, Marcello; Olive, Daniel

doi:10.1042/bj2930835

Cited by 42 publications

(25 citation statements)

References 44 publications

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“…DISCUSSION A major challenge in the study of CD28 signalling is the lack of a detectable response with the treatment of soluble bivalent anti-CD28 alone (reviewed in references 26 and 34). No calcium flux, inositol phosphate release, or significant tyrosine kinase activity occurs unless CD28 is super-cross-linked (31,42,43). Although a direct study of CD28 signalling has not been possible, two distinct events stimulated by CD28 ligation can be detected in the presence of a primary signal such as PMA: the tyrosine phosphorylation of several proteins (36,57) and the induction of the CD28RC in the nucleus (14,58).…”

Section: Resultsmentioning

confidence: 99%

Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells.

Bryan¹,

Li²,

Lai³

et al. 1994

Mol. Cell. Biol.

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Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (ReIA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of IL-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of IKBax following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel-containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling.Antigenic stimulation of T cells requires both recognition by the T-cell receptor (TCR) of the major histocompatibility complex-antigen complex and the interactions of other cell surface molecules (reviewed in reference 59). One such interaction occurs between the accessory molecule CD28 on T cells and its cognate ligands B7-1 (CD80/B7 [33]), B7-2 (2, 16), and B7-3 (BB-1 [7]) on antigen-presenting cells. The CD28 molecule (for reviews, see references 26, 34, and 48) is constitutively expressed as a 44-kDa homodimer which is present on 95% of CD4' T cells and on approximately 50 to 70% of CD8' T cells. Blocking CD28 function during T-cell activation with an antigen can drive the T cells into a long-lasting antigen-specific anergic state (18,53). Conversely, anergy induced by suboptimal stimulation of TCRs can be prevented by ligation of CD28 molecules with anti-CD28 monoclonal antibody (MAb) (23). The CD28 signalling pathway is distinct from the TCR-CD3 signalling pathway (26), as shown by the inability of the immunosuppressant cyclosporin A to block CD28 signalling (5, 27) while completely blocking TCR-CD3 signalling.CD28 signalling as mimicked by MAbs can cooperate with anti-CD2, anti-CD3, phytohemagglutinin (PHA), and phorbol myristate acetate (PMA) to upregulate T-cell responsiveness. It synergizes with these signals to induce proliferation of T cells and secretion of multiple lymphokines such as interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, gamma interferon (IFN--y), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha (34, 55). The combination of anti-CD28 and anti-CD2 MAbs (but not anti-CD3) can both enhance and prolong IL-2 receptor at-chain (IL-2Ra) gene expression (8). Anti-CD28 MAb cooperates with anti-CD3 in the induction of the human immunodeficiency virus type 1 (HIV-1) long terminal repe...

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Section: Resultsmentioning

confidence: 99%

Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells.

Bryan¹,

Li²,

Lai³

et al. 1994

Mol. Cell. Biol.

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“…Triggering of the CD28 receptor with antibodies induces phospholipase C and Ras activation (18,19). Previous studies using CD28 antibodies have suggested that PTKs involved in CD28 signal transduction include the Src kinases p56 lck and p59 fyn (20,21) and the Tec family kinase ITK/EMT (22).…”

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Signal Transduction by CD28 Costimulatory Receptor on T Cells

Nunès

Truneh

Olive

et al. 1996

Journal of Biological Chemistry

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This study compares the biochemical responses in T cells activated with the CD28 ligands B7-1 and B7-2. The patterns of tyrosine phosphorylation induced in T cells by these two CD28 ligands are identical, but clearly different from the tyrosine phosphorylation induced by the T cell receptor (TCR). The TCR regulates protein complexes mediated by the adapter Grb2 both in vivo and in vitro. In contrast, there is no apparent regulation of in vivo Grb2 complexes in response to B7-1 or B7-2. Rather, B7-1 and B7-2 both induce tyrosine phosphorylation of a different adapter protein, p62. The regulation of p62 is a unique CD28 response that is not shared with the TCR. These data indicate that B7-1 and B7-2 induce identical tyrosine kinase signal transduction pathways. The data show also that the TCR and CD28 couple to different adapter proteins, which could explain the divergence of TCR and CD28 signal transduction pathways during T cell activation.

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“…To demonstrate that PRRIV can specifically respond to CD28 downstream signals, we used the CD28-deficient mutant Jurkat T-cell clone, JF3. As the JH6.2 subclone, JF3 was selected by limiting dilution of Jurkat JA3.52 T cells (43). We used RT-PCR to control for the lack of CD28 expression in the JF3 subclone.…”

Section: Resultsmentioning

confidence: 99%

Novel CD28-Responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor α-Chain Locus

Yeh

Lécine

Nunès

et al. 2001

Molecular and Cellular Biology

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The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) critically regulates the T-cell immune response, and the α chain CD25/IL-2Rα is required for the formation of the high-affinity receptor. Tissue-specific, inducible expression of the IL-2Rα gene is regulated by at least three positive regulatory regions (PRRI, PRRII, and PRRIII), but none responded to CD28 engagement in gene reporter assays although CD28 costimulation strongly amplifies IL-2Rα gene transcription. By DNase I hypersensitivity analysis, we have identified a novel TCR-CD3- and CD28-responsive enhancer (CD28rE) located 8.5 kb 5′ of the IL-2Rα gene. PRRIV/CD28rE contains a functional CRE/TRE element required for CD28 signaling. The T-cell-specific, CD28-responsive expression of the IL-2Rα gene appears controlled through PRRIV/CD28rE by cooperation of CREB/ATF and AP-1 family transcription factors.

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Signalling through CD28 T-cell activation pathway involves an inositol phospholipid-specific phospholipase C activity

Cited by 42 publications

References 44 publications

Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells.

Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells.

Signal Transduction by CD28 Costimulatory Receptor on T Cells

Novel CD28-Responsive Enhancer Activated by CREB/ATF and AP-1 Families in the Human Interleukin-2 Receptor α-Chain Locus

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