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Gene Review

CD40LG  -  CD40 ligand

Homo sapiens

Synonyms: CD154, CD40-L, CD40L, HIGM1, IGM, ...
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Disease relevance of CD40LG


Psychiatry related information on CD40LG

  • As these cytokines have been implicated in neuronal injury, a comprehensive model of pro-inflammatory CD40 ligand and amyloid-beta initiated Alzheimer's disease pathogenesis (mediated by multiple CNS cells) is proposed [5].
  • DC were loaded on day 6 with myeloma lysate (ML) or idiotype (Id) Ag and keyhole limpet hemocyanin (KLH), induced to mature on day 7 with CD40-ligand and cryopreserved on day 9 [6].
  • Recent studies have introduced two new biomarkers, soluble CD40 ligand and ischemia-modified albumin, which may aid in both diagnostic and prognostic decision making [7].

High impact information on CD40LG


Chemical compound and disease context of CD40LG


Biological context of CD40LG

  • The phenotype frequencies for the CD40LG marker did not differ significantly between gender-conditioned intermediate-MS subgroups and controls, or between gender-conditioned disability octiles [16].
  • Using four chimeric cDNA clones obtained by 3' RACE method, the break point was identified within the intron 4 of CD40LG on X chromosome and non-coding region of chromosome 14 [17].
  • High-resolution chromosome banding revealed that this patient's karyotype is 46, X, t(X;14)(q26.3;q13.1), and FISH analysis demonstrated that the break point of the chromosomal translocation is within CD40LG [17].
  • Thus, the reciprocal translocation caused the disruption of CD40LG, resulting in defective CD40L expression in the female patient with an extremely skewed X-inactivation pattern in T cells leading to the HIGM1 phenotype [17].
  • Female hyper IgM syndrome type 1 with a chromosomal translocation disrupting CD40LG [17].

Anatomical context of CD40LG


Associations of CD40LG with chemical compounds


Physical interactions of CD40LG


Regulatory relationships of CD40LG

  • As D-Lc activated T cells upregulated CD40L, it is likely that CD40 activation of D-Lc observed herein with a fibroblast cell line stably expressing CD40L, mimics physiological interactions between dendritic cells and T cells [29].
  • Further, the addition of CD28 at 24 h failed to rescue those cells induced to die after costimulation with anti-CD3/CD40L [30].
  • Our results demonstrated that CD40L was expressed on freshly isolated lamina propria T cells from these patients and was functional to induce IL-12 and TNF production by normal monocytes, especially after IFN-gamma priming [31].
  • Interestingly, CD40L expression is down-regulated by IFN-gamma, a type 1 cytokine with antiscarring properties, and is up-regulated by the profibrogenic type 2 cytokine IL-13 [32].
  • In addition, treatment of CCR5- and CD4-transfected 293T cells with secretory products from CD40L-stimulated MDM prior to infection with a CCR5-tropic HIV-1 reporter virus led to inhibition of viral entry [33].

Other interactions of CD40LG

  • We also found that costimulation with anti-CD3/CD40L resulted in enhanced production of interleukin (IL)-10, interferon gamma, and tumor necrosis factor alpha but not IL-2 or IL-6 [30].
  • The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells [19].
  • Transfer of CD40L and OX40L was observed in all and was followed by the up-regulation of B7-1 and B7-2 [34].
  • The combination of IL-13 with CD40L augmented the expression of the Bcl-2 homologues Bcl-xL and Mcl-1, suggesting this as a possible intracellular mechanism of induced survival [35].
  • These findings demonstrate that optimal maturation of DCs requires multiple signals by TNF superfamily members that include CD40L [36].

Analytical, diagnostic and therapeutic context of CD40LG


  1. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Henn, V., Slupsky, J.R., Gräfe, M., Anagnostopoulos, I., Förster, R., Müller-Berghaus, G., Kroczek, R.A. Nature (1998) [Pubmed]
  2. Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia. Chu, P., Deforce, D., Pedersen, I.M., Kim, Y., Kitada, S., Reed, J.C., Kipps, T.J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Soluble CD40 ligand induces selective proliferation of lymphoma cells in primary mantle cell lymphoma cell cultures. Andersen, N.S., Larsen, J.K., Christiansen, J., Pedersen, L.B., Christophersen, N.S., Geisler, C.H., Jurlander, J. Blood (2000) [Pubmed]
  4. CD40-CD40 ligand interactions in oxidative stress, inflammation and vascular disease. Rizvi, M., Pathak, D., Freedman, J.E., Chakrabarti, S. Trends. Mol. Med (2008) [Pubmed]
  5. CD40 signaling and Alzheimer's disease pathogenesis. Town, T., Tan, J., Mullan, M. Neurochem. Int. (2001) [Pubmed]
  6. Clinical-grade myeloma Ag pre-loaded DC vaccines retain potency after cryopreservation. Szmania, S., Yi, Q., Cottler-Fox, M., Rosen, N.A., Freeman, J., Kordsmeier, B.J., Moreno, A., Shi, J., Barlogie, B., Tricot, G., van Rhee, F. Cytotherapy. (2005) [Pubmed]
  7. Clinical utility of biomarkers in myocardial injury. Chan, M.Y., Pronovost, P.J. Current opinion in anaesthesiology. (2004) [Pubmed]
  8. CD40/CD154 interactions at the interface of tolerance and immunity. Quezada, S.A., Jarvinen, L.Z., Lind, E.F., Noelle, R.J. Annu. Rev. Immunol. (2004) [Pubmed]
  9. Immune regulation by CD40 and its ligand GP39. Foy, T.M., Aruffo, A., Bajorath, J., Buhlmann, J.E., Noelle, R.J. Annu. Rev. Immunol. (1996) [Pubmed]
  10. The CD40 antigen and its ligand. Banchereau, J., Bazan, F., Blanchard, D., Brière, F., Galizzi, J.P., van Kooten, C., Liu, Y.J., Rousset, F., Saeland, S. Annu. Rev. Immunol. (1994) [Pubmed]
  11. CD40 ligand dysregulation in HIV infection: HIV glycoprotein 120 inhibits signaling cascades upstream of CD40 ligand transcription. Zhang, R., Fichtenbaum, C.J., Hildeman, D.A., Lifson, J.D., Chougnet, C. J. Immunol. (2004) [Pubmed]
  12. IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis. Matsumoto, M., Ra, C., Kawamoto, K., Sato, H., Itakura, A., Sawada, J., Ushio, H., Suto, H., Mitsuishi, K., Hikasa, Y., Matsuda, H. J. Immunol. (1999) [Pubmed]
  13. NF-kappaB is involved in regulation of CD40 ligand expression on Mycobacterium bovis bacillus Calmette-Guérin-activated human T cells. Méndez-Samperio, P., Ayala, H., Vázquez, A. Clin. Diagn. Lab. Immunol. (2003) [Pubmed]
  14. Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. Ghamande, S., Hylander, B.L., Oflazoglu, E., Lele, S., Fanslow, W., Repasky, E.A. Cancer Res. (2001) [Pubmed]
  15. Phase I study of recombinant human CD40 ligand in cancer patients. Vonderheide, R.H., Dutcher, J.P., Anderson, J.E., Eckhardt, S.G., Stephans, K.F., Razvillas, B., Garl, S., Butine, M.D., Perry, V.P., Armitage, R.J., Ghalie, R., Caron, D.A., Gribben, J.G. J. Clin. Oncol. (2001) [Pubmed]
  16. Analysis of a CD40 ligand dinucleotide microsatellite in multiple sclerosis. Dai, Y., Masterman, T., Huang, W., Hillert, J. Eur. J. Immunogenet. (2002) [Pubmed]
  17. Female hyper IgM syndrome type 1 with a chromosomal translocation disrupting CD40LG. Imai, K., Shimadzu, M., Kubota, T., Morio, T., Matsunaga, T., Park, Y.D., Yoshioka, A., Nonoyama, S. Biochim. Biophys. Acta (2006) [Pubmed]
  18. Human dendritic cells activated by TSLP and CD40L induce proallergic cytotoxic T cells. Gilliet, M., Soumelis, V., Watanabe, N., Hanabuchi, S., Antonenko, S., de Waal-Malefyt, R., Liu, Y.J. J. Exp. Med. (2003) [Pubmed]
  19. The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells. Mikolajczak, S.A., Ma, B.Y., Yoshida, T., Yoshida, R., Kelvin, D.J., Ochi, A. J. Exp. Med. (2004) [Pubmed]
  20. Costimulation through CD28 enhances T cell-dependent B cell activation via CD40-CD40L interaction. Klaus, S.J., Pinchuk, L.M., Ochs, H.D., Law, C.L., Fanslow, W.C., Armitage, R.J., Clark, E.A. J. Immunol. (1994) [Pubmed]
  21. CD40 ligand-activated human monocytes amplify glomerular inflammatory responses through soluble and cell-to-cell contact-dependent mechanisms. Kuroiwa, T., Lee, E.G., Danning, C.L., Illei, G.G., McInnes, I.B., Boumpas, D.T. J. Immunol. (1999) [Pubmed]
  22. CD40 ligand increases complement C3 secretion by proximal tubular epithelial cells. Castellano, G., Cappiello, V., Fiore, N., Pontrelli, P., Gesualdo, L., Schena, F.P., Montinaro, V. J. Am. Soc. Nephrol. (2005) [Pubmed]
  23. Human lung myofibroblasts as effectors of the inflammatory process: the common receptor gamma chain is induced by Th2 cytokines, and CD40 ligand is induced by lipopolysaccharide, thrombin and TNF-alpha. Doucet, C., Giron-Michel, J., Canonica, G.W., Azzarone, B. Eur. J. Immunol. (2002) [Pubmed]
  24. Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production. Robson, N.C., Phillips, D.J., McAlpine, T., Shin, A., Svobodova, S., Toy, T., Pillay, V., Kirkpatrick, N., Zanker, D., Wilson, K., Helling, I., Wei, H., Chen, W., Cebon, J., Maraskovsky, E. Blood (2008) [Pubmed]
  25. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Aruffo, A., Farrington, M., Hollenbaugh, D., Li, X., Milatovich, A., Nonoyama, S., Bajorath, J., Grosmaire, L.S., Stenkamp, R., Neubauer, M. Cell (1993) [Pubmed]
  26. The evolutionarily conserved sequence upstream of the human Ig heavy chain S gamma 3 region is an inducible promoter: synergistic activation by CD40 ligand and IL-4 via cooperative NF-kappa B and STAT-6 binding sites. Schaffer, A., Cerutti, A., Shah, S., Zan, H., Casali, P. J. Immunol. (1999) [Pubmed]
  27. CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function. Yellin, M.J., Sippel, K., Inghirami, G., Covey, L.R., Lee, J.J., Sinning, J., Clark, E.A., Chess, L., Lederman, S. J. Immunol. (1994) [Pubmed]
  28. Detection of major histocompatibility complex/human cartilage gp-39 complexes in rheumatoid arthritis synovitis as a specific and independent histologic marker. Baeten, D., Steenbakkers, P.G., Rijnders, A.M., Boots, A.M., Veys, E.M., De Keyser, F. Arthritis Rheum. (2004) [Pubmed]
  29. Activation of human dendritic cells through CD40 cross-linking. Caux, C., Massacrier, C., Vanbervliet, B., Dubois, B., Van Kooten, C., Durand, I., Banchereau, J. J. Exp. Med. (1994) [Pubmed]
  30. CD40 ligand (CD154) triggers a short-term CD4(+) T cell activation response that results in secretion of immunomodulatory cytokines and apoptosis. Blair, P.J., Riley, J.L., Harlan, D.M., Abe, R., Tadaki, D.K., Hoffmann, S.C., White, L., Francomano, T., Perfetto, S.J., Kirk, A.D., June, C.H. J. Exp. Med. (2000) [Pubmed]
  31. Hyperexpression of CD40 ligand (CD154) in inflammatory bowel disease and its contribution to pathogenic cytokine production. Liu, Z., Colpaert, S., D'Haens, G.R., Kasran, A., de Boer, M., Rutgeerts, P., Geboes, K., Ceuppens, J.L. J. Immunol. (1999) [Pubmed]
  32. Expression of CD154 (CD40 ligand) by human lung fibroblasts: differential regulation by IFN-gamma and IL-13, and implications for fibrosis. Kaufman, J., Sime, P.J., Phipps, R.P. J. Immunol. (2004) [Pubmed]
  33. Regulation of human immunodeficiency virus type 1 infection, beta-chemokine production, and CCR5 expression in CD40L-stimulated macrophages: immune control of viral entry. Cotter, R.L., Zheng, J., Che, M., Niemann, D., Liu, Y., He, J., Thomas, E., Gendelman, H.E. J. Virol. (2001) [Pubmed]
  34. Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes. Biagi, E., Dotti, G., Yvon, E., Lee, E., Pule, M., Vigouroux, S., Gottschalk, S., Popat, U., Rousseau, R., Brenner, M. Blood (2005) [Pubmed]
  35. Interleukin-13 in combination with CD40 ligand potently inhibits apoptosis in human B lymphocytes: upregulation of Bcl-xL and Mcl-1. Lømo, J., Blomhoff, H.K., Jacobsen, S.E., Krajewski, S., Reed, J.C., Smeland, E.B. Blood (1997) [Pubmed]
  36. Cooperation of TNF family members CD40 ligand, receptor activator of NF-kappa B ligand, and TNF-alpha in the activation of dendritic cells and the expansion of viral specific CD8+ T cell memory responses in HIV-1-infected and HIV-1-uninfected individuals. Yu, Q., Gu, J.X., Kovacs, C., Freedman, J., Thomas, E.K., Ostrowski, M.A. J. Immunol. (2003) [Pubmed]
  37. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. Cella, M., Scheidegger, D., Palmer-Lehmann, K., Lane, P., Lanzavecchia, A., Alber, G. J. Exp. Med. (1996) [Pubmed]
  38. B lymphocytes from patients with chronic lymphoproliferative disorders are equipped with different costimulatory molecules. Trentin, L., Zambello, R., Sancetta, R., Facco, M., Cerutti, A., Perin, A., Siviero, M., Basso, U., Bortolin, M., Adami, F., Agostini, C., Semenzato, G. Cancer Res. (1997) [Pubmed]
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