Immobilized anti-CD5 together with prolonged activation of protein kinase C induce interleukin 2-dependent T cell growth: evidence for signal transduction through CD5.
Monoclonal antibodies (mAb) identifying the CD5 antigen were used to stimulate human peripheral blood T lymphocytes. Three out of three anti-CD5 mAb, 10.2, OKT1 and anti-Leu-1 induced vigorous proliferation of purified T cells in the presence of 1.6 nM phorbol 12-myristate 13-acetate (PMA). Immobilization of anti-CD5 mAb on a solid support was necessary for the induction of a proliferative response. Neither 1.6 nM PMA, nor immobilized anti-CD5 mAb were mitogenic as a sole stimulus. mAb identifying CD4, CD7, CD11a, CD18, and major histocompatibility complex class I molecules were not comitogenic with PMA. Anti-CD5/PMA-induced cell proliferation proceeded by an interleukin 2 (IL 2)-dependent mechanism, as was demonstrated by the cell surface expression of the p55 chain of the IL 2 receptor ( IL 2R), the production of IL 2 and the inhibition of the proliferative response by anti- IL 2R mAb anti-Tac. There was no strict requirement for detectable numbers of monocytes, although cell proliferation could be enhanced by the monocyte-derived cytokines IL 1 and IL 6. Phorbol 12,13-dibutyrate and mezerein could substitute for PMA in this activation pathway, but synthetic diacylglycerols and phorbol esters that do not activate protein kinase C (PKC) could not, indicating a need for prolonged activation of PKC. T cells activated by anti-CD5/PMA are sensitive to inhibition by cyclosporin A (CsA) and by prostaglandin E2 (PGE2). This contrasts with anti-CD28/PMA-induced T cell proliferation, which is resistant to CsA and PGE2. Cell surface expression of CD5 was strongly up-regulated by PMA, whereas CD3 expression was down-regulated. We conclude that T cell activation can be triggered by engagement of CD5 by immobilized anti-CD5 mAb, combined with prolonged activation of PKC. These data support a role for CD5 as an independent signal transducing molecule.[1]References
- Immobilized anti-CD5 together with prolonged activation of protein kinase C induce interleukin 2-dependent T cell growth: evidence for signal transduction through CD5. Vandenberghe, P., Ceuppens, J.L. Eur. J. Immunol. (1991) [Pubmed]
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