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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
Majerus, P. W., E. J. Neufeld, and D. B. Wilson. 1984. Production of phosphoinositide-derived messengers. Cell 37:701–703.
Majerus, P. W., T. M. Connolly, H. Deckmyn, and T. S. Ross. 1986. The metabolism of phosphoinositol-derived messenger molecules. Science 234:1519–1526.
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.
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.
Farrar, W. L., and F. W. Ruscetti. 1986. Association of Protein Kinase C Activation With IL 2 Receptor Expression. J. Immunol. 136:1266–1273.
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.
Berney, S. M., and T. P. Atkinson. 1995. Phosphatidylinositol hydrolysis in freshly isolated human lymphocytes. J. Immunological Methods 186:71–77.
Promega Catalog. 1996. CellTiter 96 AQueous Non-Radioactive Cell Proliferation Assay. Promega Catalog 1–10.
Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 65:55–63.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kishimoto, H., and J. Sprent. 1999. Several different cell surface molecules control negative selection of medullary thymocytes. J. Exp. Med. 190:65–73.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Issue Date:
DOI: https://doi.org/10.1023/A:1010919719200