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. 1993 Aug 1;293(Pt 3):835–842. doi: 10.1042/bj2930835

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

J Nunes 1, S Klasen 1, M D Franco 1, C Lipcey 1, C Mawas 1, M Bagnasco 1, D Olive 1
PMCID: PMC1134444  PMID: 8394695

Abstract

Stimulation of the human T-cell line, Jurkat, by a monoclonal antibody (mAb) directed against the CD28 molecule leads to sustained increases in intracellular levels of Ca2+ ([Ca2+]i); the initial rise in Ca2+ comes from internal stores, followed by Ca2+ entry into the cells. The CD28 molecule also appears to activate polyphosphoinositide (InsPL)-specific phospholipase C (PLC) activity in Jurkat cells, as demonstrated by PtdInsP2 breakdown, InsP3 and 1,2-diacylglycerol generation and PtdIns resynthesis. We also observed that interleukin-2 (IL2) production induced via CD28 triggering was sensitive to a selective protein kinase C inhibitor. Of the four other anti-CD28 mAbs (CD28.2, CD28.4, CD28.5, CD28.6) tested, only one (CD28.5) was unable to generate any InsPL-specific PLC or IL2 secretion. However, the cross-linking of cell-bound CD28.5 with anti-mouse Ig antibodies led to an increase in [Ca2+]i. CD28-molecule clustering in itself appears to be a sufficient signal for induction of PLC activity.

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Selected References

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  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. Bagnasco M., Nunes J., Lopez M., Cerdan C., Pierres A., Mawas C., Olive D. T cell activation via the CD2 molecule is associated with protein kinase C translocation from the cytosol to the plasma membrane. Eur J Immunol. 1989 May;19(5):823–827. doi: 10.1002/eji.1830190507. [DOI] [PubMed] [Google Scholar]
  3. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  4. Cerdan C., Martin Y., Courcoul M., Brailly H., Mawas C., Birg F., Olive D. Prolonged IL-2 receptor alpha/CD25 expression after T cell activation via the adhesion molecules CD2 and CD28. Demonstration of combined transcriptional and post-transcriptional regulation. J Immunol. 1992 Oct 1;149(7):2255–2261. [PubMed] [Google Scholar]
  5. Dustin M. L., Sanders M. E., Shaw S., Springer T. A. Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med. 1987 Mar 1;165(3):677–692. doi: 10.1084/jem.165.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldsmith M. A., Weiss A. Early signal transduction by the antigen receptor without commitment to T cell activation. Science. 1988 May 20;240(4855):1029–1031. doi: 10.1126/science.3259335. [DOI] [PubMed] [Google Scholar]
  7. Hahn W. C., Menu E., Bothwell A. L., Sims P. J., Bierer B. E. Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Science. 1992 Jun 26;256(5065):1805–1807. doi: 10.1126/science.1377404. [DOI] [PubMed] [Google Scholar]
  8. Hara T., Fu S. M., Hansen J. A. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J Exp Med. 1985 Jun 1;161(6):1513–1524. doi: 10.1084/jem.161.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Inokuchi S., Imboden J. B. Antigen receptor-mediated regulation of sustained polyphosphoinositide turnover in a human T cell line. Evidence for a receptor-regulated pathway for production of phosphatidylinositol 4,5-bisphosphate. J Biol Chem. 1990 Apr 15;265(11):5983–5989. [PubMed] [Google Scholar]
  11. June C. H., Ledbetter J. A., Gillespie M. M., Lindsten T., Thompson C. B. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol. 1987 Dec;7(12):4472–4481. doi: 10.1128/mcb.7.12.4472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kanner S. B., Damle N. K., Blake J., Aruffo A., Ledbetter J. A. CD2/LFA-3 ligation induces phospholipase-C gamma 1 tyrosine phosphorylation and regulates CD3 signaling. J Immunol. 1992 Apr 1;148(7):2023–2029. [PubMed] [Google Scholar]
  13. Khan A. A., Steiner J. P., Snyder S. H. Plasma membrane inositol 1,4,5-trisphosphate receptor of lymphocytes: selective enrichment in sialic acid and unique binding specificity. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2849–2853. doi: 10.1073/pnas.89.7.2849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ledbetter J. A., Imboden J. B., Schieven G. L., Grosmaire L. S., Rabinovitch P. S., Lindsten T., Thompson C. B., June C. H. CD28 ligation in T-cell activation: evidence for two signal transduction pathways. Blood. 1990 Apr 1;75(7):1531–1539. [PubMed] [Google Scholar]
  15. Ledbetter J. A., June C. H., Grosmaire L. S., Rabinovitch P. S. Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1384–1388. doi: 10.1073/pnas.84.5.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lindstein T., June C. H., Ledbetter J. A., Stella G., Thompson C. B. Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science. 1989 Apr 21;244(4902):339–343. doi: 10.1126/science.2540528. [DOI] [PubMed] [Google Scholar]
  17. Linsley P. S., Clark E. A., Ledbetter J. A. T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5031–5035. doi: 10.1073/pnas.87.13.5031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lu Y., Granelli-Piperno A., Bjorndahl J. M., Phillips C. A., Trevillyan J. M. CD28-induced T cell activation. Evidence for a protein-tyrosine kinase signal transduction pathway. J Immunol. 1992 Jul 1;149(1):24–29. [PubMed] [Google Scholar]
  19. Martin P. J., Ledbetter J. A., Morishita Y., June C. H., Beatty P. G., Hansen J. A. A 44 kilodalton cell surface homodimer regulates interleukin 2 production by activated human T lymphocytes. J Immunol. 1986 May 1;136(9):3282–3287. [PubMed] [Google Scholar]
  20. Metzger H. Transmembrane signaling: the joy of aggregation. J Immunol. 1992 Sep 1;149(5):1477–1487. [PubMed] [Google Scholar]
  21. Moingeon P., Lucich J. L., McConkey D. J., Letourneur F., Malissen B., Kochan J., Chang H. C., Rodewald H. R., Reinherz E. L. CD3 zeta dependence of the CD2 pathway of activation in T lymphocytes and natural killer cells. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1492–1496. doi: 10.1073/pnas.89.4.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  23. Nunes J., Bagnasco M., Lopez M., Lipcey C., Mawas C., Olive D. Dissociation between early and late events in T cell activation mediated through CD28 surface molecule. Mol Immunol. 1991 Apr-May;28(4-5):427–435. doi: 10.1016/0161-5890(91)90156-e. [DOI] [PubMed] [Google Scholar]
  24. Nunès J., Klasen S., Ragueneau M., Pavon C., Couez D., Mawas C., Bagnasco M., Olive D. CD28 mAbs with distinct binding properties differ in their ability to induce T cell activation: analysis of early and late activation events. Int Immunol. 1993 Mar;5(3):311–315. doi: 10.1093/intimm/5.3.311. [DOI] [PubMed] [Google Scholar]
  25. O'Brien R. M., Soos M. A., Siddle K. Monoclonal antibodies to the insulin receptor stimulate the intrinsic tyrosine kinase activity by cross-linking receptor molecules. EMBO J. 1987 Dec 20;6(13):4003–4010. doi: 10.1002/j.1460-2075.1987.tb02743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pantaleo G., Olive D., Harris D., Poggi A., Moretta L., Moretta A. Signal transducing mechanisms involved in human T cell activation via surface T44 molecules. Comparison with signals transduced via the T cell receptor complex. Eur J Immunol. 1986 Dec;16(12):1639–1642. doi: 10.1002/eji.1830161228. [DOI] [PubMed] [Google Scholar]
  27. Pantaleo G., Olive D., Poggi A., Kozumbo W. J., Moretta L., Moretta A. Transmembrane signalling via the T11-dependent pathway of human T cell activation. Evidence for the involvement of 1,2-diacylglycerol and inositol phosphates. Eur J Immunol. 1987 Jan;17(1):55–60. doi: 10.1002/eji.1830170110. [DOI] [PubMed] [Google Scholar]
  28. Pantaleo G., Olive D., Poggi A., Kozumbo W. J., Moretta L., Moretta A. Transmembrane signalling via the T11-dependent pathway of human T cell activation. Evidence for the involvement of 1,2-diacylglycerol and inositol phosphates. Eur J Immunol. 1987 Jan;17(1):55–60. doi: 10.1002/eji.1830170110. [DOI] [PubMed] [Google Scholar]
  29. Park D. J., Rho H. W., Rhee S. G. CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453–5456. doi: 10.1073/pnas.88.12.5453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pierrès A., Lopez M., Cerdan C., Nunes J., Olive D., Mawas C. Triggering CD 28 molecules synergize with CD 2 (T 11.1 and T 11.2)-mediated T cell activation. Eur J Immunol. 1988 May;18(5):685–690. doi: 10.1002/eji.1830180505. [DOI] [PubMed] [Google Scholar]
  31. Rabinovitch P. S., June C. H., Grossmann A., Ledbetter J. A. Heterogeneity among T cells in intracellular free calcium responses after mitogen stimulation with PHA or anti-CD3. Simultaneous use of indo-1 and immunofluorescence with flow cytometry. J Immunol. 1986 Aug 1;137(3):952–961. [PubMed] [Google Scholar]
  32. Schreiber A. B., Libermann T. A., Lax I., Yarden Y., Schlessinger J. Biological role of epidermal growth factor-receptor clustering. Investigation with monoclonal anti-receptor antibodies. J Biol Chem. 1983 Jan 25;258(2):846–853. [PubMed] [Google Scholar]
  33. Secrist J. P., Karnitz L., Abraham R. T. T-cell antigen receptor ligation induces tyrosine phosphorylation of phospholipase C-gamma 1. J Biol Chem. 1991 Jul 5;266(19):12135–12139. [PubMed] [Google Scholar]
  34. Stohl W., Hofman F. M., Gray J. D. Differential CD3/T cell antigen receptor-mediated IL-2 production in jurkat T cells. Dissociation of IL-2 response from total inositol phosphate and calcium responses. J Immunol. 1990 Aug 15;145(4):1078–1087. [PubMed] [Google Scholar]
  35. Toullec D., Pianetti P., Coste H., Bellevergue P., Grand-Perret T., Ajakane M., Baudet V., Boissin P., Boursier E., Loriolle F. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771–15781. [PubMed] [Google Scholar]
  36. Van Lier R. A., Brouwer M., Aarden L. A. Signals involved in T cell activation. T cell proliferation induced through the synergistic action of anti-CD28 and anti-CD2 monoclonal antibodies. Eur J Immunol. 1988 Jan;18(1):167–172. doi: 10.1002/eji.1830180125. [DOI] [PubMed] [Google Scholar]
  37. Van Lier R. A., Brouwer M., De Groot E. D., Kramer I., Aarden L. A., Verhoeven A. J. T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways. Eur J Immunol. 1991 Jul;21(7):1775–1778. doi: 10.1002/eji.1830210731. [DOI] [PubMed] [Google Scholar]
  38. Vandenberghe P., Freeman G. J., Nadler L. M., Fletcher M. C., Kamoun M., Turka L. A., Ledbetter J. A., Thompson C. B., June C. H. Antibody and B7/BB1-mediated ligation of the CD28 receptor induces tyrosine phosphorylation in human T cells. J Exp Med. 1992 Apr 1;175(4):951–960. doi: 10.1084/jem.175.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Weiss A., Imboden J. B. Cell surface molecules and early events involved in human T lymphocyte activation. Adv Immunol. 1987;41:1–38. doi: 10.1016/s0065-2776(08)60029-2. [DOI] [PubMed] [Google Scholar]
  40. Weiss A., Manger B., Imboden J. Synergy between the T3/antigen receptor complex and Tp44 in the activation of human T cells. J Immunol. 1986 Aug 1;137(3):819–825. [PubMed] [Google Scholar]
  41. Weissman A. M., Bonifacino J. S., Klausner R. D., Samelson L. E., O'Shea J. J. T cell antigen receptor: structure, assembly and function. Year Immunol. 1989;4:74–93. [PubMed] [Google Scholar]
  42. Williams T. M., Moolten D. M., Makni H., Kim H. W., Kant J. A., Kamoun M. CD28-stimulated IL-2 gene expression in Jurkat T cells occurs in part transcriptionally and is cyclosporine-A sensitive. J Immunol. 1992 Apr 15;148(8):2609–2616. [PubMed] [Google Scholar]

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