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T cell activation following infection of primary follicle center lymphoma B cells with adenovirus encoding CD154

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Abstract

Purified, high-titer adenovirus encoding murine CD154 (Ad-CD154) or human CD154 (Ad-hCD154) was used to infect lymph node cells isolated from patients with follicle center lymphoma. Infection of lymphoma B cells with Ad-CD154 at a multiplicity of infection (MOI) ratio of 100 or higher resulted in high-level transgene expression. Additionally, upon infection of lymphoma B cells, only Ad-CD154 resulted in surface expression of CD154, despite similar, high-level expression of either human or mouse CD154 by HeLa cells infected with Ad-hCD154 or Ad-CD154, respectively. Moreover, infection of lymphoma B cells with Ad-CD154, but not Ad-hCD154 or adenovirus encoding Eschericheria coli beta-galactosidase (Ad-LacZ), induced the neoplastic B cells to express higher levels of immune co-stimulatory molecules that are required for proficient presentation of antigen to T cells. Consistent with this, we found that Ad-CD154 infected lymphoma B cells could stimulate T cells to proliferate or produce interferon-gamma in allogeneic or autologous mixed lymphocyte interactions. We conclude that lymphoma B cells can be infected with Ad-CD154 and that this significantly enhances their recognition by allogeneic or autologous T cells. As such, Ad-CD154-transduced lymphoma B cells may have potential for the active immune therapy of patients with follicle center lymphoma.

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References

  1. Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S . The CD40 antigen and its ligand Annu Rev Immunol 1994 12: 881–922

    Article  CAS  Google Scholar 

  2. Laman JD, Claassen E, Noelle RJ . Functions of CD40 and its ligand, gp39 (CD40L) Crit Rev Immunol 1996 16: 59–108

    Article  CAS  Google Scholar 

  3. Cantwell M, Hua T, Pappas J, Kipps TJ . Acquired CD40-ligand deficiency in chronic lymphocytic leukemia Nat Med 1997 3: 984–989

    Article  CAS  Google Scholar 

  4. Castle BE, Kishimoto K, Stearns C, Brown ML, Kehry MR . Regulation of expression of the ligand for CD40 on T helper lymphocytes J Immunol 1993 151: 1777–1788

    CAS  PubMed  Google Scholar 

  5. Hermann P, Blanchard D, de Saint-Vis B, Fossiez F, Gaillard C, Vanbervliet B, Briere F, Banchereau J, Galizzi JP . Expression of a 32-kDa ligand for the CD40 antigen on activated human T lymphocytes Eur J Immunol 1993 23: 961–964

    Article  CAS  Google Scholar 

  6. Roy M, Waldschmidt T, Aruffo A, Ledbetter JA, Noelle RJ . The regulation of the expression of gp39, the CD40 ligand, on normal and cloned CD4+ T cells J Immunol 1993 151: 2497–2510

    CAS  PubMed  Google Scholar 

  7. Ranheim EA, Kipps TJ . Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal J Exp Med 1993 177: 925–935

    Article  CAS  Google Scholar 

  8. Ranheim EA, Kipps TJ . Tumor necrosis factor-alpha facilitates induction of CD80 (B7–1) and CD54 on human B cells by activated T cells: complex regulation by IL-4, IL-10, and CD40L Cell Immunol 1995 161: 226–235

    Article  CAS  Google Scholar 

  9. Grewal IS, Flavell RA . CD40 and CD154 in cell-mediated immunity Ann Rev Immunol 1998 16: 111–135

    Article  CAS  Google Scholar 

  10. Mackey MF, Barth RJ Jr, Noelle RJ . The role of CD40/CD154 interactions in the priming, differentiation, and effector function of helper and cytotoxic T cells J Leukoc Biol 1998 63: 418–428

    Article  CAS  Google Scholar 

  11. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M . The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome Cell 1993 72: 291–300

    Article  CAS  Google Scholar 

  12. 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 361: 539–541

    Article  CAS  Google Scholar 

  13. Kato K, Cantwell MJ, Sharma S, Kipps TJ . Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells J Clin Invest 1998 101: 1133–1141

    Article  CAS  Google Scholar 

  14. Wierda WG, Cantwell MJ, Woods SJ, Rassenti LZ, Prussak CE, Kipps TJ . CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia Blood 2000 96: 2917–2924

    CAS  PubMed  Google Scholar 

  15. Dilloo D, Brown M, Roskrow M, Zhong W, Holladay M, Holden W, Brenner M . CD40 ligand induces an antileukemia immune response in vivo Blood 1997 90: 1927–1933

    CAS  PubMed  Google Scholar 

  16. Kikuchi T, Crystal RG . Anti-tumor immunity induced by in vivo adenovirus vector-mediated expression of CD40 ligand in tumor cells Hum Gene Ther 1999 10: 1375–1387

    Article  CAS  Google Scholar 

  17. Nakajima A, Kodama T, Morimoto S, Azuma M, Takeda K, Oshima H, Yoshino S, Yagita H, Okumura K . Antitumor effect of CD40 ligand: elicitation of local and systemic antitumor responses by IL-12 and B7 J Immunol 1998 161: 1901–1907

    CAS  PubMed  Google Scholar 

  18. Schultze JL, Cardoso AA, Freeman GJ, Seamon MJ, Daley J, Pinkus GS, Gribben JG, Nadler LM . Follicular lymphomas can be induced to present alloantigen efficiently: a conceptual model to improve their tumor immunogenicity (published erratum appears in Proc Natl Acad Sci USA 1995; 92: 10818) Proc Natl Acad Sci USA 1995 92: 8200–8204

    Article  CAS  Google Scholar 

  19. Schultze JL, Seamon MJ, Michalak S, Gribben JG, Nadler LM . Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro Blood 1997 89: 3806–3816

    CAS  PubMed  Google Scholar 

  20. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R . Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells Nat Med 1996 2: 52–58

    Article  CAS  Google Scholar 

  21. Renschler MF, Wada HG, Fok KS, Levy R . B-lymphoma cells are activated by peptide ligands of the antigen binding receptor or by anti-idiotypic antibody to induce extracellular acidification Cancer Res 1995 55: 5642–5647

    CAS  PubMed  Google Scholar 

  22. Cantwell MJ, Sharma S, Friedmann T, Kipps TJ . Adenovirus vector infection of chronic lymphocytic leukemia B cells Blood 1996 88: 4676–4683

    CAS  PubMed  Google Scholar 

  23. Blanche F, Cameron B, Barbot A, Ferrero L, Guillemin T, Guyot S, Somarriba S, Bisch D . An improved anion-exchange HPLC method for the detection and purification of adenoviral particles Gene Therapy 2000 7: 1055–1062

    Article  CAS  Google Scholar 

  24. Huyghe BG, Liu X, Sutjipto S, Sugarman BJ, Horn MT, Shepard HM, Scandella CJ, Shabram P . Purification of a type 5 recombinant adenovirus encoding human p53 by column chromatography Hum Gene Ther 1995 6: 1403–1416

    Article  CAS  Google Scholar 

  25. Shabram PW, Giroux DD, Goudreau AM, Gregory RJ, Horn MT, Huyghe BG, Liu X, Nunnally MH, Sugarman BJ, Sutjipto S . Analytical anion-exchange HPLC of recombinant type-5 adenoviral particles Hum Gene Ther 1997 8: 453–465

    Article  CAS  Google Scholar 

  26. Becker TC, Noel RJ, Coats WS, Gómez-Foix AM, Alam T, Gerard RD, Newgard CB . Use of recombinant adenovirus for metabolic engineering of mammalian cells Meth Cell Biol 1994 43: 161–189

    Article  CAS  Google Scholar 

  27. Blossom S, Chu EB, Weigle WO, Gilbert KM . CD40 ligand expressed on B cells in the BXSB mouse model of systemic lupus erythematosus J Immunol 1997 159: 4580–4586

    CAS  PubMed  Google Scholar 

  28. Clodi K, Asgary Z, Zhao S, Kliche KO, Cabanillas F, Andreeff M, Younes A . Coexpression of CD40 and CD40 ligand in B-cell lymphoma cells Br J Haematol 1998 103: 270–275

    Article  CAS  Google Scholar 

  29. Desai-Mehta A, Lu L, Ramsey-Goldman R, Datta SK . Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production J Clin Invest 1996 97: 2063–2073

    Article  CAS  Google Scholar 

  30. Schattner EJ, Mascarenhas J, Reyfman I, Koshy M, Woo C, Friedman SM, Crow MK . Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T-cell type costimulatory capacity Blood 1998 91: 2689–2697

    CAS  PubMed  Google Scholar 

  31. Kato K, Santana-Sahagún E, Rassenti LZ, Weisman MH, Tamura N, Kobayashi S, Hashimoto H, Kipps TJ . The soluble CD40 ligand sCD154 in systemic lupus erythematosus J Clin Invest 1999 104: 947–955

    Article  CAS  Google Scholar 

  32. Younes A, Snell V, Consoli U, Clodi K, Zhao S, Palmer JL, Thomas EK, Armitage RJ, Andreeff M . Elevated levels of biologically active soluble CD40 ligand in the serum of patients with chronic lymphocytic leukaemia Br J Haematol 1998 100: 135–141

    Article  CAS  Google Scholar 

  33. Lane P, Traunecker A, Hubele S, Inui S, Lanzavecchia A, Gray D . Activated human T cells express a ligand for the human B cell-associated antigen CD40 which participates in T cell-dependent activation of B lymphocytes Eur J Immunol 1992 22: 2573–2578

    Article  CAS  Google Scholar 

  34. Andersen NS, Larsen JK, Christiansen J, Pedersen LB, Christophersen NS, Geisler CH, Jurlander J . Soluble CD40 ligand induces selective proliferation of lymphoma cells in primary mantle cell lymphoma cell cultures Blood 2000 96: 2219–2225

    CAS  PubMed  Google Scholar 

  35. Funakoshi S, Longo DL, Beckwith M, Conley DK, Tsarfaty G, Tsarfaty I, Armitage RJ, Fanslow WC, Spriggs MK, Murphy WJ . Inhibition of human B-cell lymphoma growth by CD40 stimulation Blood 1994 83: 2787–2794

    CAS  PubMed  Google Scholar 

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Acknowledgements

These studies funded in part by PO1-CA81534, PO1-CA34233, and PO1-CA72103 from the NIH

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Authors and Affiliations

  1. Immunogenex, Inc., La Jolla, CA, USA

    MJ Cantwell, WG Wierda, IS Lossos, R Levy & TJ Kipps

  2. Division of Oncology, Stanford University Medical School, Stanford, CA, USA

    MJ Cantwell, WG Wierda, IS Lossos, R Levy & TJ Kipps

  3. Division of Hematology/Oncology, UCSD School of Medicine, La Jolla, CA, USA

    MJ Cantwell, WG Wierda, IS Lossos & R Levy

  4. Division of Hematology/Oncology, Department of Medicine, University of Californai-San Diego, 9500 Gilman Dr., La Jolla, CA, 92093-0663, USA

    TJ Kipps

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Cantwell, M., Wierda, W., Lossos, I. et al. T cell activation following infection of primary follicle center lymphoma B cells with adenovirus encoding CD154. Leukemia 15, 1451–1457 (2001). https://doi.org/10.1038/sj.leu.2402208

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  • DOI: https://doi.org/10.1038/sj.leu.2402208

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