CD27–CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell development

• Published in: International immunology 2007-06, Vol.19 (6), p.713-718
• Main Authors: van Oosterwijk, Michiel F., Juwana, Hedi, Arens, Ramon, Tesselaar, Kiki, van Oers, Marinus H. J., Eldering, Eric, van Lier, René A. W.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, CD - genetics; Antigens, CD - metabolism; bcl-X Protein - genetics; bcl-X Protein - metabolism; CD27; CD27 Ligand - genetics; CD27 Ligand - metabolism; CD3 Complex - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD70; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Proliferation - drug effects; Flow Cytometry; Gene Expression Profiling; Humans; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-12 - pharmacology; Interleukin-12 Receptor beta 2 Subunit - genetics; Interleukin-12 Receptor beta 2 Subunit - metabolism; Interleukin-4 - metabolism; Interleukin-4 - pharmacology; Mice; Protein Binding; T cell differentiation; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - metabolism; TNF-R family members; Transfection; Tumor Necrosis Factor Receptor Superfamily, Member 7 - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxm033

Stimulation of CD27, a member of the tumour necrosis factor receptor family, by its ligand CD70 induces expansion of IFNγ secreting CD4+ and CD8+ T cells in vivo. We here analysed the mechanisms through which CD27 mediates this effect. CD27 co-stimulation induced cell division but did not directly instruct naive CD4+ T cells to differentiate into IFNγ-producing Th1 cells. Rather, in concert with signals delivered through the TCR–CD3 complex, CD27 co-stimulation enhanced the Th1-specific transcription factor T-bet and caused up-regulation of the IL-12Rbeta2 chain. Consequently, CD27-costimulated T cells yielded vast numbers of IFNγ-secreting cells in response to IL-12. Additionally, CD27 ligation induced a strong up-regulation of Bcl-xL, but not of related anti-apoptotic molecules. Thus, CD27–CD70 interactions may promote Th1 formation by permitting naive T cells to respond to differentiation signals and by promoting survival of activated effector T cells.