CD27 is a signal-transducing molecule involved in CD45RA+ naive T cell costimulation.
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.
Kobata
T
T
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115.
Agematsu
K
K
Kameoka
J
J
Schlossman
S F
SF
Morimoto
C
C
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D007376:Interleukin-2; D010835:Phytohemagglutinins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium