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J Immunol. 1994 Dec 15;153(12):5422-32.

CD27 is a signal-transducing molecule involved in CD45RA+ naive T cell costimulation.

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  • 1Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115.

Abstract

CD27 is a 120-kDa transmembrane homodimeric molecule expressed on the majority of T cells, B cells, and NK cells that belongs to the TNFR/nerve growth factor receptor family. The interaction between CD27 and its ligand, CD70, is thought to play an important role in T cell activation. In this paper we have examined the signal-transducing potential of CD27 in T cell costimulation. Anti-CD27 mAb, anti-1A4, induced substantial proliferation of peripheral blood T cells in the presence of a suboptimal dose of PMA, phytohemagglutinin, anti-CD2, or anti-CD3 together with a second Ab to cross-link the CD27 molecule. This T cell proliferation was also observed by using CD70 transfectant cells. CD27 cross-linking maximally induced proliferation of CD45RA+CD4 T cells but only slightly induced proliferation of CD45RO+CD4 T cells. CD27-mediated T cell proliferation did not seem to be dependent on the IL-2/IL-2R system because no detectable level of IL-2 was secreted, and only a partial inhibition was observed with anti-IL-2 and anti-IL-2R Abs. Furthermore, an increase in intracellular Ca2+ was observed in PMA-treated T cells when the CD27 molecule was cross-linked. More importantly, CD27 ligation induced protein tyrosine phosphorylation, especially 70 kDa of cellular substrate, including ZAP-70, in T cells. Herbimycin A, a protein tyrosine kinase inhibitor, and staurosporine, a protein kinase C inhibitor, blocked T cell proliferation induced by CD27 ligation, suggesting the possibility that the activation of protein tyrosine kinase and protein kinase C is required for CD27-mediated T cell costimulation. These results clearly demonstrate that the CD27/CD70 interaction induces costimulatory signals in T cells, especially CD45RA+ naive T cells, indicating that CD27 serves as a T cell signal-transducing molecule.

PMID:
7989747
[PubMed - indexed for MEDLINE]
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