Abstract
CD40-CD40-ligand (CD154) interactions play a critical role in immune activation. Using replication defective adenovirus encoding mouse CD154 (Ad-CD154), we modified human chronic lymphocytic leukemia B cells to express a functional ligand for CD40. This not only induces expression of immune accessory molecules on the infected cell, but also allows it to trans-activate noninfected bystander leukemia B cells. Also, factors that impair the antigen-presenting capacity of leukemia B cells are downmodulated. Ad-CD154- infected leukemia cells are highly effective stimulators in mixed lymphocyte reactions and can induce generation of cytotoxic T lymphocytes specific for autologous nonmodified leukemia cells. As such, Ad-CD154 can induce a host antileukemia response that may have therapeutic potential.
Full Text
The Full Text of this article is available as a PDF (321.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aguilar-Santelises M., Rottenberg M. E., Lewin N., Mellstedt H., Jondal M. Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression. Int J Cancer. 1996 Apr 22;69(2):114–119. doi: 10.1002/(SICI)1097-0215(19960422)69:2<114::AID-IJC8>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
- Armitage R. J., Fanslow W. C., Strockbine L., Sato T. A., Clifford K. N., Macduff B. M., Anderson D. M., Gimpel S. D., Davis-Smith T., Maliszewski C. R. Molecular and biological characterization of a murine ligand for CD40. Nature. 1992 May 7;357(6373):80–82. doi: 10.1038/357080a0. [DOI] [PubMed] [Google Scholar]
- Banchereau J., Bazan F., Blanchard D., Brière F., Galizzi J. P., van Kooten C., Liu Y. J., Rousset F., Saeland S. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881–922. doi: 10.1146/annurev.iy.12.040194.004313. [DOI] [PubMed] [Google Scholar]
- Banchereau J., de Paoli P., Vallé A., Garcia E., Rousset F. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science. 1991 Jan 4;251(4989):70–72. doi: 10.1126/science.1702555. [DOI] [PubMed] [Google Scholar]
- Bigler R. D., Bushkin Y., Chiorazzi N. S152 (CD27). A modulating disulfide-linked T cell activation antigen. J Immunol. 1988 Jul 1;141(1):21–28. [PubMed] [Google Scholar]
- Caligaris-Cappio F. B-chronic lymphocytic leukemia: a malignancy of anti-self B cells. Blood. 1996 Apr 1;87(7):2615–2620. [PubMed] [Google Scholar]
- Cantwell M. J., Sharma S., Friedmann T., Kipps T. J. Adenovirus vector infection of chronic lymphocytic leukemia B cells. Blood. 1996 Dec 15;88(12):4676–4683. [PubMed] [Google Scholar]
- Cantwell M., Hua T., Pappas J., Kipps T. J. Acquired CD40-ligand deficiency in chronic lymphocytic leukemia. Nat Med. 1997 Sep;3(9):984–989. doi: 10.1038/nm0997-984. [DOI] [PubMed] [Google Scholar]
- Cardoso A. A., Schultze J. L., Boussiotis V. A., Freeman G. J., Seamon M. J., Laszlo S., Billet A., Sallan S. E., Gribben J. G., Nadler L. M. Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen. Blood. 1996 Jul 1;88(1):41–48. [PubMed] [Google Scholar]
- Castle B. E., Kishimoto K., Stearns C., Brown M. L., Kehry M. R. Regulation of expression of the ligand for CD40 on T helper lymphocytes. J Immunol. 1993 Aug 15;151(4):1777–1788. [PubMed] [Google Scholar]
- Chen L., Ashe S., Brady W. A., Hellström I., Hellström K. E., Ledbetter J. A., McGowan P., Linsley P. S. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell. 1992 Dec 24;71(7):1093–1102. doi: 10.1016/s0092-8674(05)80059-5. [DOI] [PubMed] [Google Scholar]
- Clark E. A., Ledbetter J. A. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4494–4498. doi: 10.1073/pnas.83.12.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark E. A., Ledbetter J. A. How B and T cells talk to each other. Nature. 1994 Feb 3;367(6462):425–428. doi: 10.1038/367425a0. [DOI] [PubMed] [Google Scholar]
- Dranoff G., Jaffee E., Lazenby A., Golumbek P., Levitsky H., Brose K., Jackson V., Hamada H., Pardoll D., Mulligan R. C. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3539–3543. doi: 10.1073/pnas.90.8.3539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Durie F. H., Foy T. M., Masters S. R., Laman J. D., Noelle R. J. The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today. 1994 Sep;15(9):406–411. doi: 10.1016/0167-5699(94)90269-0. [DOI] [PubMed] [Google Scholar]
- Finn W. G., Thangavelu M., Yelavarthi K. K., Goolsby C. L., Tallman M. S., Traynor A., Peterson L. C. Karyotype correlates with peripheral blood morphology and immunophenotype in chronic lymphocytic leukemia. Am J Clin Pathol. 1996 Apr;105(4):458–467. doi: 10.1093/ajcp/105.4.458. [DOI] [PubMed] [Google Scholar]
- Gimmi C. D., Freeman G. J., Gribben J. G., Gray G., Nadler L. M. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6586–6590. doi: 10.1073/pnas.90.14.6586. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodwin R. G., Alderson M. R., Smith C. A., Armitage R. J., VandenBos T., Jerzy R., Tough T. W., Schoenborn M. A., Davis-Smith T., Hennen K. Molecular and biological characterization of a ligand for CD27 defines a new family of cytokines with homology to tumor necrosis factor. Cell. 1993 May 7;73(3):447–456. doi: 10.1016/0092-8674(93)90133-b. [DOI] [PubMed] [Google Scholar]
- Grewal I. S., Foellmer H. G., Grewal K. D., Xu J., Hardardottir F., Baron J. L., Janeway C. A., Jr, Flavell R. A. Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. Science. 1996 Sep 27;273(5283):1864–1867. doi: 10.1126/science.273.5283.1864. [DOI] [PubMed] [Google Scholar]
- Hermann P., Blanchard D., de Saint-Vis B., Fossiez F., Gaillard C., Vanbervliet B., Brière F., Banchereau J., Galizzi J. P. Expression of a 32-kDa ligand for the CD40 antigen on activated human T lymphocytes. Eur J Immunol. 1993 Apr;23(4):961–964. doi: 10.1002/eji.1830230430. [DOI] [PubMed] [Google Scholar]
- Inaba M., Inaba K., Fukuba Y., Mori S., Haruna H., Doi H., Adachi Y., Iwai H., Hosaka N., Hisha H. Activation of thymic B cells by signals of CD40 molecules plus interleukin-10. Eur J Immunol. 1995 May;25(5):1244–1248. doi: 10.1002/eji.1830250517. [DOI] [PubMed] [Google Scholar]
- Johnson T. A., Rassenti L. Z., Kipps T. J. Ig VH1 genes expressed in B cell chronic lymphocytic leukemia exhibit distinctive molecular features. J Immunol. 1997 Jan 1;158(1):235–246. [PubMed] [Google Scholar]
- Kayagaki N., Kawasaki A., Ebata T., Ohmoto H., Ikeda S., Inoue S., Yoshino K., Okumura K., Yagita H. Metalloproteinase-mediated release of human Fas ligand. J Exp Med. 1995 Dec 1;182(6):1777–1783. doi: 10.1084/jem.182.6.1777. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koduru P. R., Lichtman S. M., Smilari T. F., Sun T., Goh J. C., Karp L., Hall W., Hashimoto S., Chiorazzi N., Broome J. D. Serial phenotypic, cytogenetic and molecular genetic studies in Richter's syndrome: demonstration of lymphoma development from the chronic lymphocytic leukaemia cells. Br J Haematol. 1993 Nov;85(3):613–616. doi: 10.1111/j.1365-2141.1993.tb03357.x. [DOI] [PubMed] [Google Scholar]
- Koopman G., Reutelingsperger C. P., Kuijten G. A., Keehnen R. M., Pals S. T., van Oers M. H. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. 1994 Sep 1;84(5):1415–1420. [PubMed] [Google Scholar]
- Lane P., Brocker T., Hubele S., Padovan E., Lanzavecchia A., McConnell F. Soluble CD40 ligand can replace the normal T cell-derived CD40 ligand signal to B cells in T cell-dependent activation. J Exp Med. 1993 Apr 1;177(4):1209–1213. doi: 10.1084/jem.177.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lishner M., Lalkin A., Klein A., Yarkoni S., Manor Y., Fejgin M., Leytin V., Ravid M., Amiel A. The BCL-1, BCL-2, and BCL-3 oncogenes are involved in chronic lymphocytic leukemia. Detection by fluorescence in situ hybridization. Cancer Genet Cytogenet. 1995 Dec;85(2):118–123. doi: 10.1016/0165-4608(95)00152-2. [DOI] [PubMed] [Google Scholar]
- Noelle R. J., Roy M., Shepherd D. M., Stamenkovic I., Ledbetter J. A., Aruffo A. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6550–6554. doi: 10.1073/pnas.89.14.6550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parham P., Barnstable C. J., Bodmer W. F. Use of a monoclonal antibody (W6/32) in structural studies of HLA-A,B,C, antigens. J Immunol. 1979 Jul;123(1):342–349. [PubMed] [Google Scholar]
- Ranheim E. A., Cantwell M. J., Kipps T. J. Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Blood. 1995 Jun 15;85(12):3556–3565. [PubMed] [Google Scholar]
- Ranheim E. A., Kipps T. J. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. J Exp Med. 1993 Apr 1;177(4):925–935. doi: 10.1084/jem.177.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ranheim E. A., Kipps T. J. 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 Apr 1;161(2):226–235. doi: 10.1006/cimm.1995.1031. [DOI] [PubMed] [Google Scholar]
- Rassenti L. Z., Kipps T. J. Lack of allelic exclusion in B cell chronic lymphocytic leukemia. J Exp Med. 1997 Apr 21;185(8):1435–1445. doi: 10.1084/jem.185.8.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roy M., Waldschmidt T., Aruffo A., Ledbetter J. A., Noelle R. J. The regulation of the expression of gp39, the CD40 ligand, on normal and cloned CD4+ T cells. J Immunol. 1993 Sep 1;151(5):2497–2510. [PubMed] [Google Scholar]
- Schultze J. L., Seamon M. J., Michalak S., Gribben J. G., Nadler L. M. Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro. Blood. 1997 May 15;89(10):3806–3816. [PubMed] [Google Scholar]
- Schwartz R. H. A cell culture model for T lymphocyte clonal anergy. Science. 1990 Jun 15;248(4961):1349–1356. doi: 10.1126/science.2113314. [DOI] [PubMed] [Google Scholar]
- Spriggs M. K., Armitage R. J., Strockbine L., Clifford K. N., Macduff B. M., Sato T. A., Maliszewski C. R., Fanslow W. C. Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. J Exp Med. 1992 Dec 1;176(6):1543–1550. doi: 10.1084/jem.176.6.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tan P., Anasetti C., Hansen J. A., Melrose J., Brunvand M., Bradshaw J., Ledbetter J. A., Linsley P. S. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med. 1993 Jan 1;177(1):165–173. doi: 10.1084/jem.177.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Townsend S. E., Allison J. P. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science. 1993 Jan 15;259(5093):368–370. doi: 10.1126/science.7678351. [DOI] [PubMed] [Google Scholar]
- Vermes I., Haanen C., Steffens-Nakken H., Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 1995 Jul 17;184(1):39–51. doi: 10.1016/0022-1759(95)00072-i. [DOI] [PubMed] [Google Scholar]
- Watson A. J., DeMars R., Trowbridge I. S., Bach F. H. Detection of a novel human class II HLA antigen. 1983 Jul 28-Aug 3Nature. 304(5924):358–361. doi: 10.1038/304358a0. [DOI] [PubMed] [Google Scholar]
- Yang Y., Wilson J. M. CD40 ligand-dependent T cell activation: requirement of B7-CD28 signaling through CD40. Science. 1996 Sep 27;273(5283):1862–1864. doi: 10.1126/science.273.5283.1862. [DOI] [PubMed] [Google Scholar]