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CD5 (OKT1) Augments CD3-Mediated Intracellular Signaling Events in Human T Lymphocytes

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Abstract

CD5 is expressed on thymocytes, all mature T cells, and a subset of mature B cells, and probably contributes to T-cell–B-cell adhesion. We assessed whether CD5-crosslinking by mAb augments T-cell stimulation. Plate-bound anti-CD5 or anti-CD3 mAb alone had no effect on any of the assessed activation parameters of resting T cells. However, concomitant signaling through both CD5 and CD3 by plate-bound antibodies resulted in marked increases in T-cell surface CD69 expression and T-cell metabolism, as assessed by the T cell's ability to reduce 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) to formazen. In addition, simultaneous cross-linking of CD5 and CD3 caused a significant (p < 0.001) increase in phosphatidylinositol hydrolysis in resting T cells compared to stimulation with anti-CD3 mAb alone or anti-CD3 mAb plus anti-CD5 isotype control antibody. These results indicate that CD5 augments signaling through CD3 and consequently functions as a costimulatory molecule for resting T cells.

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References

  1. Van de Velde, H., I. von Hoegen, W. Luo, J. R. Parnes, and K. Thielemans. 1991. The B-cell surface protein CD72 ?Lyb-2 is the ligand for CD5. Nature 351:662–664.

    Google Scholar 

  2. Pospisil, R., M. G. Fitts, and R. G. Mage. 1996. CD5 is a potential selecting ligand for B cell surface immunoglobulin framework region sequences. J. Exp. Med. 184:1279–1284.

    Google Scholar 

  3. Bikah, G., F. M. Lynd, A. A. Aruffo, J. A. Ledbetter, and S. Bondada. 1998. A role for CD5 in cognate interactions between T cells and B cells, and identification of a novel ligand for CD5. Int. Immunol. 10:1185–1196.

    Google Scholar 

  4. Muthukkumar, S., and S. Bondada. 1995. Involvement of CD5 in Th1 and Th2 contact-mediated rescue of anti-mu and ionomycin induced growth inhibition in a B cell lymphoma. Int. Immunol. 7:305–315.

    Google Scholar 

  5. Burgess, K. E., M. Yamamoto, K. V. S. Prasad, and C. E. Rudd. 1992. CD5 acts as a tyrosine kinase substrate within a receptor complex comprising T-cell receptor zeta chain ?CD3 and proteintyrosine kinase p56lck and p59 fyn. Proc. Natl. Acad. Sci. USA 89:9311–9315.

    Google Scholar 

  6. Cooper, P. H., and J. M. Hawthorne. 1976. Phosphatidylinositol kinase and diphosphonositide kinase of rat kidney cortex properties and subcellular localization. Biochem. J. 160:97–105.

    Google Scholar 

  7. Majerus, P. W., E. J. Neufeld, and D. B. Wilson. 1984. Production of phosphoinositide-derived messengers. Cell 37:701–703.

    Google Scholar 

  8. Majerus, P. W., T. M. Connolly, H. Deckmyn, and T. S. Ross. 1986. The metabolism of phosphoinositol-derived messenger molecules. Science 234:1519–1526.

    Google Scholar 

  9. Imboden, J. B., and A. Weiss. 1987. The T-cell antigen receptor regulates sustained increases in cytoplasmic free Ca2+ through extracellular Ca2+ influx and ongoing intracellular Ca2+ mobilization. Biochem. J. 247:695–700.

    Google Scholar 

  10. Manger, B., A. Weiss, J. Imboden, T. Laing, and J. D. Stobo. 1987. The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex effects of stimulation with soluble or immobilized CD3 antibodies. J. Immunol. 139:2755–2760.

    Google Scholar 

  11. Farrar, W. L., and F. W. Ruscetti. 1986. Association of Protein Kinase C Activation With IL 2 Receptor Expression. J. Immunol. 136:1266–1273.

    Google Scholar 

  12. Testi, R., D. D'Ambrosio, R. De Maria, and A. Santoni. 1994. The CD69 receptor: a multipurpose cell-surface trigger for hematopoietic cells. Immunol. Today 15:479–483.

    Google Scholar 

  13. Berney, S. M., and T. P. Atkinson. 1995. Phosphatidylinositol hydrolysis in freshly isolated human lymphocytes. J. Immunological Methods 186:71–77.

    Google Scholar 

  14. Promega Catalog. 1996. CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay. Promega Catalog 1–10.

  15. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 65:55–63.

    Google Scholar 

  16. Atkinson, T. P., M. A. Kaliner, and R. J. Hohman. 1992. Phospholipase C-Gamma1 is translocated to the membrane of rat basophilic leukemia cells in response to aggregation of IgE receptors. J. Immunol. 148: 2194–2200.

    Google Scholar 

  17. Shimizu, Y., G. A. van Seventer, K. J. Horgan, and S. Shaw. 1990. Costimulation of Proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J. Immunol. 145:59–67.

    Google Scholar 

  18. Vandenberghe, P., J. Verwilghen, F. van Vaeck, and J. L. Ceuppens. 1993. Ligation of the CD5 or CD28 molecules on resting human T cells induces expression of the early activation antigen CD69 by a calcium-and tyrosine kinase-dependent mechanism. Immunology 78:210–217.

    Google Scholar 

  19. Imboden, J. B., C. H. June, M. A. McCutcheon, and J. A. Ledbetter. 1990. Stimulation of CD5 enhances signal transduction by the T cell antigen receptor. J. Clin. Invest. 85:130–134.

    Google Scholar 

  20. June, C. H., P. S. Rabinovitch, and J. A. Ledbetter. 1987. CD5 Antibodies increase intracellular ionized calcium concentration in T cells. J. Immunol. 138: 2782–2792.

    Google Scholar 

  21. Tarakhovsky, A., S. B. Kanner, J. Hombach, J. A. Ledbetter, W. Muller, N. Killeen, and K. Rajewsky. 1995. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 269:535–537.

    Google Scholar 

  22. Carmo, A. M., M. A. A. Castro, and F. A. Arosa. 1999. CD2 and CD3 Associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells. J. Immunol. 163:4238–4245.

    Google Scholar 

  23. Alberola-Ila, J., L. Places, D. A. Cantrell, J. Vives, and F. Lozano. 1992. Intracellular events involved in CD5-induced human T cell activation and proliferation. J. Immunol. 148:1287–1293.

    Google Scholar 

  24. Simarro, M., C. Pelassy, J. Calvo, L. Places, C. Aussel, and F. Lozano. 1997. The cytoplasmic domain of CD5 mediates both TCR ?CD3-dependent and-independent diacylglycerol production. J. Immunol. 159:4307–4315.

    Google Scholar 

  25. Gary-Gouy, H., V. Lang, S. Sarun, L. Boumsell, and G. Bismuth. 1997. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. J. Immunol. 159:3739–3747.

    Google Scholar 

  26. Calvo, J., J. M. Vilda, L. Places, M. Simarro, O. Padilla, D. Andreu, D. S. Campbell, C. Aussel, and F. Lozano. 1998. Human CD5 signaling and constitutive phosphorylation of C-terminal serine residues by casein kinase II. J. Immunol. 161:6022–6029.

    Google Scholar 

  27. Zhou, X.-Y., Y. Yashiro-Ohtani, K. Toyo-Oka, C.-S. Park, X.-G. Tai, T. Hamaoka, and H. Fujiwara. 2000. CD5 costimulation upregulates the signaling to extracellular signal-regulated kinase activation in CD4+CD8+ thymocytes and supports their differentiation to the CD4 lineage. J. Immunol. 164:1260–1268.

    Google Scholar 

  28. Kishimoto, H., and J. Sprent. 1999. Several different cell surface molecules control negative selection of medullary thymocytes. J. Exp. Med. 190:65–73.

    Google Scholar 

  29. Chan, S., C. Waltzinger, A. Tarakhovsky, C. Benoist, and D. Mathis. 1999. An influence of CD5 on the selection of CD4-lineage T cells. Eur. J. Immunol. 29:2916–2922.

    Google Scholar 

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Berney, S.M., Schaan, T., Wolf, R.E. et al. CD5 (OKT1) Augments CD3-Mediated Intracellular Signaling Events in Human T Lymphocytes. Inflammation 25, 215–221 (2001). https://doi.org/10.1023/A:1010919719200

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