Abstract
CD137 (4-1BB) is an inducible T cell co-stimulatory receptor and belongs to tumor necrosis factor receptor superfamily (TNFRSF9). In addition to its expression on activated T cells (Kwon andWeissman, 1989; Pollok et al., 1993), it is also expressed on other lymphocytes, including activated NK cells (Melero et al., 1998), NK T cells (Kwon et al., 2000) and CD4+CD25+ regulatory T cells (Gavin et al., 2002; McHugh et al., 2002), as well as myeloid cells, such as monocytes, neutrophils, and dendritic cells (Futagawa et al., 2002; Heinisch et al., 2000; Kwon et al., 1997; Wilcox et al., 2002a). CD137L (4-1BBL), a member of TNF superfamily (TNFSF9), has been detected on professional antigen presenting cells (APCs) such as B cells, macrophages, and dendritic cells (Alderson et al., 1994; Goodwin et al., 1993; Pollok et al., 1994). This type of expression pattern indicates CD137/CD137L interactions may play a role in multiple steps in various innate and adaptive immune responses.
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References
Adorini, L., and Sinigaglia, F. (1997). Pathogenesis and immunotherapy of autoimmune diseases. Immunol. Today, 18, 209–211.
Alderson, M.R., Smith, C.A., Tough, T.W., Davis-Smith, T., Armitage, R.J., Falk, B., Roux, E., Baker, E., Sutherland, G. R., and Din, W. S. (1994). Molecular and biological characterization of human 4-1BB and its ligand. Eur. J. Immunol., 24, 2219–2227.
Blazar, B.R., Kwon, B.S., Panoskaltsis-Mortari, A., Kwak, K.B., Peschon, J.J., and Taylor, P.A. (2001). Ligation of 4-1BB (CDw137) regulates graft-versus-host disease, graft- versus-leukemia, and graft rejection in allogeneic bone marrow transplant recipients. J. Immunol., 166, 3174–3183.
Bora, N.S., Kim, M.C., Kabeer, N.H., Simpson, S.C., Tandhasetti, M.T., Cirrito, T.P., Kaplan, A.D., and Kaplan, H.J. (1995). Experimental autoimmune anterior uveitis. Induction with melanin-associated antigen from the iris and ciliary body. Invest. Ophthalmol. Vis. Sci., 36, 1056–1066.
Broekhuyse, R.M., Kuhlmann, E.D., and Winkens, H.J. (1992). Experimental autoimmune anterior uveitis (EAAU). II. Dose-dependent induction and adoptive transfer using a melanin-bound antigen of the retinal pigment epithelium. Exp. Eye. Res., 55, 401–411.
Cady, S.G., and Sono, M. (1991). 1-Methyl-DL-tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2, 3-dioxygenase. Arch. Biochem. Biophys., 291, 326–333.
Chan, O.T., Madaio, M.P., and Shlomchik, M.J. (1999). The central and multiple roles of B cells in lupus pathogenesis. Immunol. Rev., 169, 107–121.
Chen, F., Maldonado, M.A., Madaio, M., and Eisenberg, R.A. (1998). The role of host (endogenous) T cells in chronic graft-versus-host autoimmune disease. J. Immunol., 161, 5880–5885.
Cohen, P.L., and Eisenberg, R.A. (1991). Lpr and gld: Single gene models of systemic autoimmunity and lymphoproliferative disease. Annu. Rev. Immunol., 9, 243–269.
DeBenedette, M.A., Chu, N.R., Pollok, K.E., Hurtado, J., Wade, W.F., Kwon, B.S., and Watts, T.H. (1995). Role of 4-1BB ligand in costimulation of T lymphocyte growth and its upregulation on M12 B lymphomas by cAMP. J. Exp. Med., 181, 985–992.
De Benedette, M.A., Wen, T., Bachmann, M.F., Ohashi, P.S., Barber, B.H., Stocking, K.L., Peschon, J.J., and Watts, T.H. (1999). Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. J. Immunol., 163, 4833–4841.
Deshpande, S.P., Lee, S., Zheng, M., Song, B., Knipe, D., Kapp, J.A., and Rouse, B.T. (2001). Herpes simplex virus-induced keratitis: Evaluation of the role of molecular mimicry in lesion pathogenesis. J. Virol., 75, 3077–3088.
Ding, A.H., Nathan, C.F., and Stuehr, D.J. (1988). Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J. Immunol., 141, 2407–2412.
Donoso, L.A., Merryman, C.F., Sery, T., Sanders, R., Vrabec, T., and Fong, S.L. (1989). Human interstitial retinoid binding protein. A potent uveitopathogenic agent for the induction of experimental autoimmune uveitis. J. Immunol., 143, 79–83.
Fallarino, F., Grohmann, U., Hwang, K.W., Orabona, C., Vacca, C., Bianchi, R., Belladonna, M.L., Fioretti, M.C., Alegre, M.L., and Puccetti, P. (2003). Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol., 4, 1206–1212.
Feldmann, M., Brennan, F.M., and Maini, R.N. (1996). Rheumatoid arthritis. Cell, 85, 307–310.
Foell, J., Strahotin, S., O’Neil, S.P., McCausland, M. M., Suwyn, C., Haber, M., Chander, P.N., Bapat, A.S., Yan, X.J., Chiorazzi, N., et al. (2003). CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB × NZW F1 mice. J. Clin. Invest., 111, 1505–1518.
Foell, J.L., Diez-Mendiondo, B.I., Diez, O.H., Holzer, U., Ruck, P., Bapat, A.S., Hoffmann, M.K., Mittler, R.S., and Dannecker, G.E. (2004). Engagement of the CD137 (4-1BB) costimulatory molecule inhibits and reverses the autoimmune process in collagen-induced arthritis and establishes lasting disease resistance. Immunology, 113, 89–98.
Futagawa, T., Akiba, H., Kodama, T., Takeda, K., Hosoda, Y., Yagita, H., and Okumura, K. (2002). Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells. Int. Immunol., 14, 275–286.
Gavin, M.A., Clarke, S.R., Negrou, E., Gallegos, A., Rudensky, A., and Howard Hughes Medical Institute, U. o. W. B. S. W. A. U. S. A. m. u. w. e. (2002). Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nature. Immunol., 3(1), 33–41.
Gery, I., Wiggert, B., Redmond, T.M., Kuwabara, T., Crawford, M.A., Vistica, B.P., and Chader, G.J. (1986). Uveoretinitis and pinealitis induced by immunization with interphotoreceptor retinoid-binding protein. Invest. Ophthalmol. Vis. Sci., 27, 1296–1300.
Gonatas, N.K., Greene, M.I., and Waksman, B.H. (1986). Genetic and molecular aspects of demyelination. Immunol. Today, 7, 121–126.
Goodwin, R.G., Din, W.S., Davis-Smith, T., Anderson, D.M., Gimpel, S.D., Sato, T.A., Maliszewski, C.R., Brannan, C.I., Copeland, N.G., Jenkins, N.A., et al. (1993). Molecular cloning of a ligand for the inducible T cell gene 4-1BB: A member of an emerging family of cytokines with homology to tumor necrosis factor. Eur. J. Immunol., 23, 2631–2641.
Grohmann, U., Orabona, C., Fallarino, F., Vacca, C., Calcinaro, F., Falorni, A., Candeloro, P., Belladonna, M.L., Bianchi, R., Fioretti, M.C., and Puccetti, P. (2002). CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol., 3, 1097–1101.
Haendeler, J., Zeiher, A.M., and Dimmeler, S. (1999). Nitric oxide and apoptosis. Vitam. Horm., 57, 49–77.
Halstead, E.S., Mueller, Y.M., Altman, J.D., and Katsikis, P.D. (2002). In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses. Nat. Immunol., 3, 536–541.
Heinisch, I.V., Daigle, I., Knopfli, B., and Simon, H.U. (2000). CD137 activation abrogates granulocyte-macrophage colony-stimulating factor-mediated anti-apoptosis in neutrophils. Eur. J. Immunol., 30, 3441–3446.
Hochberg, M.C., Boyd, R.E., Ahearn, J.M., Arnett, F.C., Bias, W.B., Provost, T.T., and Stevens, M.B. (1985). Systemic lupus erythematosus: A review of clinico-laboratory features and immunogenetic markers in 150 patients with emphasis on demographic subsets. Medicine (Baltimore), 64, 285–295.
Humbert, M., and Galanaud, P. (1990). [B-lymphocyte hyperreactivity and differentiation factors of T-lymphocytes in systemic lupus erythematosus]. Ann. Med. Interne., (Paris), 141, 213–216.
Hurtado, J.C., Kim, S.H., Pollok, K.E., Lee, Z.H., and Kwon, B.S. (1995). Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28. J. Immunol., 155, 3360–3367.
Hurtado, J.C., Kim, Y.J., and Kwon, B.S. (1997). Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death. J. Immunol., 158, 2600–2609.
Izui, S., Kelley, V.E., Masuda, K., Yoshida, H., Roths, J.B., and Murphy, E.D. (1984). Induction of various autoantibodies by mutant gene lpr in several strains of mice. J. Immunol., 133, 227–233.
Jevnikar, A.M., Grusby, M.J., and Glimcher, L.H. (1994). Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice. J. Exp. Med., 179, 1137–1143.
Jung, H.W., Choi, S.W., Choi, J.I., and Kwon, B.S. (2004). Serum concentrations of soluble 4-1BB and 4-1BB ligand correlated with the disease severity in rheumatoid arthritis. Exp. Mol. Med., 36, 13–22.
Kienzle, G., and von Kempis, J. (2000). CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes. Int. Immunol., 12, 73–82.
Kim, J., Choi, W.S., La, S., Suh, J.H., Kim, B.S., Cho, H.R., Kwon, B.S., and Kwon, B. (2005). Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells. Blood, 105, 2206–2213.
Koh, D.R., Ho, A., Rahemtulla, A., Fung-Leung, W.P., Griesser, H., and Mak, T.W. (1995). Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells. Eur. J. Immunol., 25, 2558–2562.
Kwon, B.S., and Weissman, S.M. (1989). cDNA sequences of two inducible T-cell genes. Proc. Natl. Acad. Sci. USA, 86, 1963–1967.
Kwon, B.S., Tan, K.B., Ni, J., Oh, K.O., Lee, Z.H., Kim, K.K., Kim, Y.J., Wang, S., Gentz, R., Yu, G.L., et al. (1997). A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation. J. Biol. Chem., 272, 14272–14276.
Kwon, B., Moon, C.H., Kang, S., Seo, S.K., and Kwon, B.S. (2000). 4-1BB: Still in the midst of darkness. Mol. Cells., 10, 119–126.
Kwon, B.S., Hurtado, J.C., Lee, Z.H., Kwack, K.B., Seo, S.K., Choi, B.K., Koller, B.H., Wolisi, G., Broxmeyer, H.E., and Vinay, D.S. (2002). Immune responses in 4-1BB (CD137)-deficient mice. J. Immunol., 168, 5483–5490.
Lanzavecchia, A., and Sallusto, F. (2000). Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science, 290, 92–97.
Liblau, R.S., Singer, S.M., and McDevitt, H.O. (1995). Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol. Today, 16, 34–38.
Luross, J.A., and Williams, N.A. (2001). The genetic and immunopathological processes underlying collagen-induced arthritis. Immunology., 103, 407–416.
Maldonado, M.A., Eisenberg, R.A., Roper, E., Cohen, P.L., and Kotzin, B.L. (1995). Greatly reduced lymphoproliferation in lpr mice lacking major histocompatibility complex class I. J. Exp. Med., 181, 641–648.
McHugh, R.S., Whitters, M.J., Piccirillo, C.A., Young, D.A., Shevach, E.M., Collins, M., Byrne, M.C., Cellular Immunology Section, L. o. I. N. I. o. A., and Infectious Diseases, N. I. o. H. B. M. D., USA (2002). CD4(+)CD25(+) immunoregulatory T cells: Gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity, 16(2), 311–323.
Melero, I., Shuford, W.W., Newby, S.A., Aruffo, A., Ledbetter, J.A., Hellstrom, K.E., Mittler, R.S., and Chen, L. (1997). Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat. Med., 3, 682–685.
Melero, I., Johnston, J.V., Shufford, W.W., Mittler, R.S., and Chen, L. (1998). NK1.1 cells express 4-1BB (CDw137) costimulatory molecule and are required for tumor immunity elicited by anti-4-1BB monoclonal antibodies. Cell. Immunol., 190, 167–172.
Mellor, A.L., Sivakumar, J., Chandler, P., Smith, K., Molina, H., Mao, D., and Munn, D.H. (2001). Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat. Immunol., 2, 64–68.
Mellor, A.L., Baban, B., Chandler, P., Marshall, B., Jhaver, K., Hansen, A., Koni, P.A., Iwashima, M., and Munn, D.H. (2003). Cutting edge: Induced indoleamine 2, 3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J. Immunol., 171, 1652–1655.
Michel, J., Langstein, J., Hofstadter, F., and Schwarz, H. (1998). A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by activated lymphocytes and is detectable in sera of patients with rheumatoid arthritis. Eur. J. Immunol., 28, 290–295.
Mittler, R.S., Bailey, T.S., Klussman, K., Trailsmith, M.D., and Hoffmann, M. K. (1999). Anti-4-1BB monoclonal antibodies abrogate T cell-dependent humoral immune responses in vivo through the induction of helper T cell anergy. J. Exp. Med., 190, 1535–1540.
Morris, S.C., Cheek, R.L., Cohen, P.L., and Eisenberg, R.A. (1990). Autoantibodies in chronic graft versus host result from cognate T-B interactions. J. Exp. Med., 171, 503–517.
Morse, H.C., 3rd, Davidson, W.F., Yetter, R.A., Murphy, E.D., Roths, J.B., and Coffman, R.L. (1982). Abnormalities induced by the mutant gene Ipr: Expansion of a unique lymphocyte subset. J. Immunol., 129, 2612–2615.
Munn, D.H., Zhou, M., Attwood, J.T., Bondarev, I., Conway, S.J., Marshall, B., Brown, C., and Mellor, A.L. (1998). Prevention of allogeneic fetal rejection by tryptophan catabolism. Science, 281, 1191–1193.
Munn, D.H., Shafizadeh, E., Attwood, J.T., Bondarev, I., Pashine, A., and Mellor, A.L. (1999). Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med., 189, 1363–1372.
Myers, L.K., Rosloniec, E.F., Cremer, M.A., and Kang, A.H. (1997). Collagen-induced arthritis, an animal model of autoimmunity. Life. Sci., 61, 1861–1878.
Myers, L., Takahashi, C., Mittler, R.S., Rossi, R.J., and Vella, A.T. (2003). Effector CD8 T cells possess suppressor function after 4-1BB and Toll-like receptor triggering. Proc. Natl. Acad. Sci., USA, 100, 5348–5353.
Palmer, D.G. (1995). The anatomy of the rheumatoid lesion. Br. Med. Bull., 51, 286–295.
Pollok, K.E., Kim, Y.J., Zhou, Z., Hurtado, J., Kim, K.K., Pickard, R.T., and Kwon, B. S. (1993). Inducible T cell antigen 4-1BB. Analysis of expression and function. J. Immunol., 150, 771–781.
Pollok, K.E., Kim, Y.J., Hurtado, J., Zhou, Z., Kim, K.K., and Kwon, B.S. (1994). 4-1BB T-cell antigen binds to mature B cells and macrophages, and costimulates anti-mu-primed splenic B cells. Eur. J. Immunol., 24, 367–374.
Ranges, G.E., Sriram, S., and Cooper, S.M. (1985). Prevention of type II collagen-induced arthritis by in vivo treatment with anti-L3T4. J. Exp. Med., 162, 1105–1110.
Rizzo, L.V., Morawetz, R.A., Miller-Rivero, N.E., Choi, R., Wiggert, B., Chan, C.C., Morse, H.C., 3rd, Nussenblatt, R.B., and Caspi, R.R. (1999). IL-4 and IL-10 are both required for the induction of oral tolerance. J. Immunol., 162, 2613–2622.
Rosen, S.D. (2004). Ligands for L-selectin: Homing, inflammation, and beyond. Annu. Rev. Immunol., 22, 129–156.
Russell, R.G., Nasisse, M.P., Larsen, H.S., and Rouse, B.T. (1984). Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis. Invest. Ophthalmol. Vis. Sci., 25, 938–944.
Schwarz, H., Blanco, F. J., von Kempis, J., Valbracht, J., and Lotz, M. (1996). ILA, a member of the human nerve growth factor/tumor necrosis factor receptor family, regulates T-lymphocyte proliferation and survival. Blood, 87, 2839–2845.
Seki, N., Sudo, Y., Yoshioka, T., Sugihara, S., Fujitsu, T., Sakuma, S., Ogawa, T., Hamaoka, T., Senoh, H., and Fujiwara, H. (1988). Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity. J. Immunol., 140, 1477–1484.
Seo, S.K., Park, H.Y., Choi, J.H., Kim, W.Y., Kim, Y.H., Jung, H.W., Kwon, B., Lee, H.W., and Kwon, B.S. (2003). Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis. J. Immunol., 171, 576–583.
Seo, S.K., Choi, J.H., Kim, Y.H., Kang, W.J., Park, H.Y., Suh, J.H., Choi, B.K., Vinay, D.S., and Kwon, B.S. (2004). 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat. Med., 10, 1088–1094.
Setareh, M., Schwarz, H., and Lotz, M. (1995). A mRNA variant encoding a soluble form of 4-1BB, a member of the murine NGF/TNF receptor family. Gene, 164, 311–315.
Shao, H., Fu, Y., Liao, T., Peng, Y., Chen, L., Kaplan, H.J., and Sun, D. (2005). Anti-CD137 mAb treatment inhibits experimental autoimmune uveitis by limiting expansion and increasing apoptotic death of uveitogenic T cells. Invest. Ophthalmol. Vis. Sci., 46, 596–603.
Sharief, M.K. (2002). Heightened intrathecal release of soluble CD137 in patients with multiple sclerosis. Eur. J. Neurol., 9, 49–54.
Shuford, W.W., Klussman, K., Tritchler, D.D., Loo, D.T., Chalupny, J., Siadak, A.W., Brown, T.J., Emswiler, J., Raecho, H., Larsen, C.P., et al. (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.
Sobel, E.S., Kakkanaiah, V.N., Kakkanaiah, M., Cheek, R.L., Cohen, P.L., and Eisenberg, R.A. (1994). T-B collaboration for autoantibody production in lpr mice is cognate and MHC-restricted. J. Immunol., 152, 6011–6016.
Sun, Y., Chen, H.M., Subudhi, S.K., Chen, J., Koka, R., Chen, L., and Fu, Y.X. (2002a). Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nat. Med., 8, 1405–1413.
Sun, Y., Lin, X., Chen, H.M., Wu, Q., Subudhi, S.K., Chen, L., and Fu, Y.X. (2002b). Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of experimental autoimmune encephalomyelitis. J. Immunol., 168, 1457–1465.
Sytwu, H.K., Lin, W.D., Roffler, S.R., Hung, J.T., Sung, H.S., Wang, C.H., Cheng, T.L., Tsou, S.C., Hsi, S.C., and Shen, K.L. (2003). Anti-4-1BB-based immunotherapy for autoimmune diabetes: Lessons from a transgenic non-obese diabetic (NOD) model. J. Autoimmun., 21, 247–254.
Takahashi, C., Mittler, R.S., and Vella, A.T. (1999). Cutting edge: 4-1BB is a bona fide CD8 T cell survival signal. J. Immunol., 162, 5037–5040.
Tan, J.T., Whitmire, J.K., Ahmed, R., Pearson, T.C., and Larsen, C.P. (1999). 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J. Immunol., 163, 4859–4868.
Tan, J.T., Whitmire, J.K., Murali-Krishna, K., Ahmed, R., Altman, J.D., Mittler, R.S., Sette, A., Pearson, T.C., and Larsen, C.P. (2000). 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. J. Immunol., 164, 2320–2325.
Tarrant, T.K., Silver, P.B., Chan, C.C., Wiggert, B., and Caspi, R.R. (1998). Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis. J. Immunol., 161, 122–127.
Taylor, P.C., Plater-Zyberk, C., and Maini, R.N. (1995). The role of the B cells in the adoptive transfer of collagen-induced arthritis from DBA/1 (H-2q) to SCID (H-2d) mice. Eur. J. Immunol., 25, 763–769.
Theofilopoulos, A.N., and Dixon, F.J. (1981). Etiopathogenesis of murine SLE. Immunol. Rev., 55, 179–216.
Theofilopoulos, A.N., and Dixon, F.J. (1985). Murine models of systemic lupus erythematosus. Adv. Immunol., 37, 269–390.
Tuohy, V.K., Yu, M., Yin, L., Kawczak, J.A., Johnson, J.M., Mathisen, P.M., Weinstock-Guttman, B., and Kinkel, R.P. (1998). The epitope spreading cascade during progression of experimental autoimmune encephalomyelitis and multiple sclerosis. Immunol. Rev., 164, 93–100.
van Rappard-Van der Veen, F.M., Kiesel, U., Poels, L., Schuler, W., Melief, C.J., Landegent, J., and Gleichmann, E. (1984). Further evidence against random polyclonal antibody formation in mice with lupus-like graft-vs-host disease. J. Immunol., 132, 1814–1820.
Vanderlugt, C.L., Neville, K.L., Nikcevich, K.M., Eagar, T.N., Bluestone, J.A., and Miller, S.D. (2000). Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J. Immunol., 164, 670–678.
Vogelsang, G.B. (2001). How I treat chronic graft-versus-host disease. Blood, 97, 1196–1201.
Wacker, W.B., Donoso, L.A., Kalsow, C.M., Yankeelov, J.A., Jr., and Organisciak, D.T. (1977). Experimental allergic uveitis. Isolation, characterization, and localization of a soluble uveitopathogenic antigen from bovine retina. J. Immunol., 119, 1949–1958.
Wekerle, H. (1991). Immunopathogenesis of multiple sclerosis. Acta. Neurol., (Napoli), 13, 197–204.
Wilcox, R.A., Chapoval, A.I., Gorski, K.S., Otsuji, M., Shin, T., Flies, D.B., Tamada, K., Mittler, R.S., Tsuchiya, H., Pardoll, D.M., and Chen, L. (2002a). Cutting edge: Expression of functional CD137 receptor by dendritic cells. J. Immunol., 168, 4262–4267.
Wilcox, R.A., Flies, D.B., Zhu, G., Johnson, A.J., Tamada, K., Chapoval, A.I., Strome, S.E., Pease, L.R., and Chen, L. (2002b). Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J. Clin. Invest., 109, 651–659.
Wildner, G., and Thurau, S.R. (1995). Orally induced bystander suppression in experimental autoimmune uveoretinitis occurs only in the periphery and not in the eye. Eur. J. Immunol., 25, 1292–1297.
Williams, M.S., Noguchi, S., Henkart, P.A., and Osawa, Y. (1998). Nitric oxide synthase plays a signaling role in TCR-triggered apoptotic death. J. Immunol., 161, 6526–6531.
Wofsy, D., Hardy, R.R., and Seaman, W.E. (1984). The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on “helper” T cells that is involved in the response to class II major histocompatibility antigens. J. Immunol., 132, 2686–2689.
Yu, M., Johnson, J.M., and Tuohy, V.K. (1996). A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: A basis for peptide-specific therapy after onset of clinical disease. J. Exp. Med., 183, 1777–1788.
Zhu, G., Flies, D.B., Tamada, K., Sun, Y., Rodriguez, M., Fu, Y.X., and Chen, L. (2001). Progressive depletion of peripheral B lymphocytes in 4-1BB (CD137) ligand/I-Ealpha)-transgenic mice. J. Immunol., 167, 2671–2676.
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Sun, Y., Fu, YX. (2006). Autoimmune Diseases. In: Chen, L. (eds) CD137 Pathway: Immunology and Diseases. Springer, Boston, MA. https://doi.org/10.1007/0-387-32829-7_7
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