OX40 Signals during Priming on Dendritic Cells Inhibit CD4 T Cell Proliferation: IL-4 Switches off OX40 Signals Enabling Rapid Proliferation of Th2 Effectors

• Published in: The Journal of immunology (1950) 2005-02, Vol.174 (3), p.1433-1437
• Main Authors: Kim, Mi-Yeon, Bekiaris, Vasilios, McConnell, Fiona M, Gaspal, Fabrina M. C, Raykundalia, Chandra, Lane, Peter J. L
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD3 Complex - metabolism; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Division - genetics; Cell Division - immunology; Cell Proliferation; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - metabolism; Down-Regulation - immunology; Growth Inhibitors - antagonists & inhibitors; Growth Inhibitors - physiology; Interleukin-4 - physiology; Ligands; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - biosynthesis; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Receptors, OX40; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - physiology; Signal Transduction - genetics; Signal Transduction - immunology; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism; Tumor Necrosis Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.3.1433

In this study we examined the role and regulation of OX40 signals during CD4 T cell priming on dendritic cells (DCs). Contrary to expectation, OX40-deficient cells proliferated more rapidly than their normal counterparts, particularly when stimulated with peptide in the absence of added cytokines. This proliferative advantage was not apparent for Th2-differentiated cells. When the reasons for this were investigated, we found that the cytokine IL-4 specifically down-regulated expression of OX40 ligand on T, B, and DCs, but not on the CD4(+)CD3(-) cells linked with selection of Th2 cells into the memory compartment. OX40 ligand expression was also down-regulated on rapidly proliferating Th1 effectors. These data are compatible with OX40 signals acting during priming as a check on naive T cell proliferation while T cells integrate additional DC signals. This would serve to limit inappropriate T cell responses. In contrast, OX40 signals from CD4(+)CD3(-) cells located in the outer T zone select proliferating Th2 effectors into the memory T cell pool.