CD137 Signal Transduction
T lymphocytes have critical roles in clearing cells expressing foreign antigens. The proliferation of T cells and their differentiation into effector and memory cells confers T cell-mediated adaptive immunity (Abbas et al., 1997). To undertake these antigen-specific functions, T cells require two signals: ligation of the T cell receptor (TCR) by the MHC/peptide complex on the antigen presenting cell (APC), and cross-linking of co-stimulatory receptors on the T cell with corresponding ligands on the APC (Carreno and Collins, 2002; Chambers and Allison, 1999). In addition, cytokines synthesized and released by the APC can modulate T cell functions in a paracrine way (Beginat et al., 2003; Kanegane and Tosato 1996; Lantz et al., 2000; Lodolce et al., 1998; Nakajima et al., 1997; Schluns et al., 2000; Unutmaz et al., 1994; Unutmaz et al., 1995; Zhang et al., 1998). Although the exact mechanisms by which several co-stimulatory molecules can interact to stimulate T cells remain to be uncovered, co-stimulation appears to be an accurate process that subtly evokes T cell immunity (Rothstein and Sayegh, 2003; Samia and Mohamed, 2004; Van Parijs, and Abbas, 1998). Co-stimulatory signals determine whether antigen-priming T cells become fully activated or antigen-specifically inactivated (Samia and Mohamed, 2004). If the concentration of antigen or its affinity for TCR is low, co-stimulatory signals tend to enhance antigen-specific TCR signals and fully activate T cells by activating their own signaling pathways or enhancing those generated by the TCR (Gravestein et al., 1998; Kenneth and Thompson, 2002). Co-stimulation can promote both early antigen-priming T cell activation and late T cell differentiation to effector or memory cells (Michael, 2003). At the same time, negative co-stimulatory signals may prevent unnecessary activation of T cells and hence autoimmune responses (Rothstein and Sayegh, 2003; Samia and Mohamed, 2004).
Unable to display preview. Download preview PDF.
- Abbas, A.K., Lichtman, A.H., and Pober, J.S. (1997). Cellular and Molecular Immunology. W.B. Saunders, Philadelphia, Pennsylvania.Google Scholar
- Appleman, L.J., van Puijenbroek, A.A. F.L., Shu, K.M., Nadler, L.M., and Boussiotis, V.A. (2002). CD28 costimulation mediates down-regulation of p27kip1 and cell cycle progression by activating of the PI3K/PKB signaling pathway in primary human T cells. J. Immunol., 168, 2729–2736.PubMedGoogle Scholar
- Bertram, E.M., Lau, P., and Watts, T.W. (2002). Temporal segregation of 4-1BB versus CD28-mediated costimulation: 4-1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection. J. Immunol., 168, 3777–3785.PubMedGoogle Scholar
- Brown, T.J., Emswiler, J., Raecho, H., Larsen, C.P., Pearson, T.C., Ledbetter, J.A., Aruffo, A., and Mittler. R.S. (1997). 4-1BB costimulatory signals preferentially induce CD8 T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J. Exp. Med., 186, 47–55.PubMedCrossRefGoogle Scholar
- Jones, R., Parsons, G.M., Bonnard, M., Chan, V.S.F., Yeh, W.-C., Woodgett, J.R., and Ohashi, P.S. (2000). Protein kinase B regulates T lymphocyte survival, nuclear factor κ B activation, and Bcl-XL levels in vivo. J. Exp. Med. 191, 1721–1734.Google Scholar
- Shuford, W.W., Klussman, K., Tritchler, D.D., Loo, D.K., Chalupny, J., Siadak, A.W., Brown, T.J., Emswiler, J., Raecho, H., Larsen, C.P., Pearson, T.C., Ledbetter, J.A., Aruffo, A., and Mittler, R.S. (1997). 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J. Exp. Med., 186, 46–55.CrossRefGoogle Scholar