Skip to main content

Advertisement

Log in

The role of platelet CD154 in the modulation in adaptive immunity

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Platelets’ primary role is hemostasis. However, a growing body of research has demonstrated that platelets are integral to the initiation of an inflammatory response and are potent effector cells of the innate immune response. Activated platelets express CD154, a molecule critical to adaptive immune responses, which has been implicated in platelet-mediated modulation of innate immune responses and inflammation. Recent studies utilizing CD154 knockout mice extend the role of platelet-derived CD154 to the modulation of adaptive immune response by enhancing antigen presentation, improving CD8+ T cell responses, and playing a critical function in T-dependent humoral immunity under physiological conditions. Together these data provide a basis for the expansion of the current paradigm of B cell activation and germinal center formation to include a role for platelets.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Litman GW, Cannon JP, Dishaw LJ. Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol 2005;11:866–79.

    Article  CAS  Google Scholar 

  2. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M et al. The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell 1993;2:291–300.

    Article  Google Scholar 

  3. Korthauer U, Graf D, Mages HW, Briere F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature 1993;6412:539–41.

    Article  Google Scholar 

  4. DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature 1993;6412:541–3.

    Article  Google Scholar 

  5. Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK et al. CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science 1993;5097:990–3.

    Article  Google Scholar 

  6. Kawabe T, Naka T, Yoshida K, Tanaka T, Fujiwara H, Suematsu S, Yoshida N, Kishimoto T, Kikutani H. The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1994;3:167–78.

    Article  Google Scholar 

  7. Xu J, Foy TM, Laman JD, Elliott EA, Dunn JJ, Waldschmidt TJ, Elsemore J, Noelle RJ, Flavell RA. Mice deficient for the CD40 ligand. Immunity 1994;5:423–31.

    Article  Google Scholar 

  8. Renshaw BR, Fanslow WC III, Armitage RJ, Campbell KA, Liggitt D, Wright B, Davison BL, Maliszewski CR. Humoral immune responses in CD40 ligand-deficient mice. J Exp Med 1994;5:1889–900.

    Article  Google Scholar 

  9. Cunningham-Rundles C, Ponda PP. Molecular defects in T- and B-cell primary immunodeficiency diseases. Nat Rev Immunol 2005;11:880–92.

    Article  CAS  Google Scholar 

  10. Medzhitov R, Janeway CA Jr. Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 1997;1:4–9.

    Article  Google Scholar 

  11. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;6673:245–52.

    Article  CAS  Google Scholar 

  12. Redmond WL, Sherman LA. Peripheral tolerance of CD8 T lymphocytes. Immunity 2005;3:275–84.

    Article  CAS  Google Scholar 

  13. Steinman RM, Hemmi H. Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol 2006;311:17–58.

    Article  PubMed  CAS  Google Scholar 

  14. Fujii S, Liu K, Smith C, Bonito AJ, Steinman RM. The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med 2004;12:1607–18.

    Article  Google Scholar 

  15. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, Kroczek RA. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998;6667:591–4.

    Google Scholar 

  16. Elzey BD, Tian J, Jensen RJ, Swanson AK, Lees JR, Lentz SR, Stein CS, Nieswandt B, Wang Y, Davidson BL, Ratliff TL. Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity 2003;1:9–19.

    Article  Google Scholar 

  17. Kaneider NC, Kaser A, Tilg H, Ricevuti G, Wiedermann CJ. CD40 ligand-dependent maturation of human monocyte-derived dendritic cells by activated platelets. Int J Immunopathol Pharmacol 2003;3:225–31.

    Google Scholar 

  18. Czapiga M, Kirk AD, Lekstrom-Himes J. Platelets deliver costimulatory signals to antigen-presenting cells: a potential bridge between injury and immune activation. Exp Hematol 2004;2:135–9.

    Article  CAS  Google Scholar 

  19. Elzey BD, Grant JF, Sinn HW, Nieswandt B, Waldschmidt TJ, Ratliff TL. Cooperation between platelet-derived CD154 and CD4+ T cells for enhanced germinal center formation. J Leukoc Biol 2005;1:80–4.

    Article  CAS  Google Scholar 

  20. van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol 2000;1:2–17.

    Google Scholar 

  21. Elzey BD, Sprague DL, Ratliff TL. The emerging role of platelets in adaptive immunity. Cell Immunol 2005;1:1–9.

    Article  CAS  Google Scholar 

  22. Siemens DR, Austin JC, Hedican SP, Tartaglia J, Ratliff TL. Viral vector delivery in solid-state vehicles: gene expression in a murine prostate cancer model. J Natl Cancer Inst 2000;5:403–412.

    Article  Google Scholar 

  23. Wilner G. Aggregation of platelets by collagen. J Clin Investing 1968;2616–2621.

  24. Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 1998;6684:480–3.

    Article  CAS  Google Scholar 

  25. van Stipdonk MJB, Hardenberg G, Bijker MS, Lemmens EE, Droin NM, Green DR, Schoenberger SP. Dynamic programming of CD8+ T lymphocyte responses. 2003;4:361–5.

  26. Masopust D, Ahmed R. Reflections on CD8 T-cell activation and memory. Immunol Res 2004;1–3:151–60.

    Article  Google Scholar 

  27. Masopust D, Kaech SM, Wherry EJ, Ahmed R. The role of programming in memory T-cell development. Curr Opin Immunol 2004;2:217–25.

    Article  CAS  Google Scholar 

  28. Ochs HD, Hollenbaugh D, Aruffo A. The role of CD40L (gp39)/CD40 in T/B cell interaction and primary immunodeficiency. Semin Immunol 1994;5:337–41.

    Article  Google Scholar 

  29. Bhushan A, Covey LR. CD40:CD40L interactions in X-linked and non-X-linked hyper-IgM syndromes. Immunol Res 2001;3:311–24.

    Article  Google Scholar 

  30. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore) 2003;6:373–84.

    Google Scholar 

  31. Agematsu K, Nagumo H, Shinozaki K, Hokibara S, Yasui K, Terada K, Kawamura N, Toba T, Nonoyama S, Ochs HD, Komiyama A. Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome. J Clin Invest 1998;4:853–60.

    Google Scholar 

  32. Klinger MH. Platelets and inflammation. Anat Embryol (Berl) 1997;1:1–11.

    Article  Google Scholar 

  33. Solanilla A, Pasquet JM, Viallard JF, Contin C, Grosset C, Dechanet-Merville J, Dupouy M, Landry M, Belloc F, Nurden P, Blanco P, Moreau JF, Pellegrin JL, Nurden AT, Ripoche J. Platelet-associated CD154 in immune thrombocytopenic purpura. Blood 2005;1:215–8.

    Article  CAS  Google Scholar 

  34. Klinger MH, Jelkmann W. Role of blood platelets in infection and inflammation. J Interferon Cytokine Res 2002;9:913–22.

    Article  Google Scholar 

  35. Weyrich AS, Lindemann S, Zimmerman GA. The evolving role of platelets in inflammation. J Thromb Haemost 2003;9:1897–905.

    Article  Google Scholar 

  36. Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol 2004;9:489–95.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by National Institutes of Health Grants AI060924.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Timothy L. Ratliff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sprague, D.L., Sowa, J.M., Elzey, B.D. et al. The role of platelet CD154 in the modulation in adaptive immunity. Immunol Res 39, 185–193 (2007). https://doi.org/10.1007/s12026-007-0074-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-007-0074-3

Keywords

Navigation