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Science 27 September 1996:
Vol. 273. no. 5283, pp. 1862 - 1864
DOI: 10.1126/science.273.5283.1862
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Reports

CD40 Ligand-Dependent T Cell Activation: Requirement of B7-CD28 Signaling Through CD40

Yiping Yang and James M. Wilson *

The role of CD40 ligand (CD40L) in the primary activation of T cells is not clear. The cellular and humoral immune responses to adenoviral vectors in a murine model of liver-directed gene transfer were studied to define the mechanisms responsible for CD40L-dependent T cell priming. CD40L-deficient mice did not develop effective cytotoxic T cells to transduced hepatocytes, and T cell-dependent B cell responses were absent. Full reconstitution of cellular and humoral immunity was achieved in CD40L-deficient mice by administration of an activating antibody to CD40 that increased expression of B7.2 on spleen cells. Wild-type mice could be made nonresponsive to vector by administration of antibodies to B7. Thus, CD40L-dependent activation of T cells occurs through signaling of CD40 in the antigen-presenting cell to enhance requisite costimulatory pathways that include B7.

Y. Yang, Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
J. M. Wilson, Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania Medical Center, and the Wistar Institute, Philadelphia, PA 19104, USA.
*   To whom correspondence should be addressed at Institute for Human Gene Therapy, Wistar Institute, Room 204, 3601 Spruce Street, Philadelphia, PA 19104-4268, USA.

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CD28, IL-2-Independent Costimulatory Pathways for CD8 T Lymphocyte Activation.
H. Sepulveda, A. Cerwenka, T. Morgan, and R. W. Dutton (1999)
J. Immunol. 163, 1133-1142
   Abstract »    Full Text »    PDF »
CD4-Mediated Signals Induce T Cell Dysfunction In Vivo.
N. Chirmule, A. Avots, S. M. L. Tamma, S. Pahwa, and E. Serfling (1999)
J. Immunol. 163, 644-649
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Implication of Interfering Antibody Formation and Apoptosis as Two Different Mechanisms Leading to Variable Duration of Adenovirus-Mediated Transgene Expression in Immune-Competent Mice.
D. B. Schowalter, C. L. Himeda, B. L. Winther, C. B. Wilson, and M. A. Kay (1999)
J. Virol. 73, 4755-4766
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T Cell Costimulatory Blockade: New Therapies for TransplantRejection.
H. GUDMUNDSDOTTIR and L. A. TURKA (1999)
J. Am. Soc. Nephrol. 10, 1356-1365
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Enhanced Expression of CD80 (B7-1), CD86 (B7-2), and CD40 and Their Ligands CD28 and CD154 in Fulminant Hepatic Failure.
L. Leifeld, C. Trautwein, F. L. Dumoulin, M. P. Manns, T. Sauerbruch, and U. Spengler (1999)
Am. J. Pathol. 154, 1711-1720
   Abstract »    Full Text »    PDF »
CD40-CD40 Ligand Interaction Is Central to Cell-Mediated Immunity Against Toxoplasma gondii: Patients with Hyper IgM Syndrome Have a Defective Type 1 Immune Response That Can Be Restored by Soluble CD40 Ligand Trimer.
C. S. Subauste, M. Wessendarp, R. U. Sorensen, and L. E. Leiva (1999)
J. Immunol. 162, 6690-6700
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Pancreatic Infiltration But Not Diabetes Occurs in the Relative Absence of MHC Class II-Restricted CD4 T Cells: Studies Using NOD/CIITA-Deficient Mice.
C. Mora, F. S. Wong, C.-H. Chang, and R. A. Flavell (1999)
J. Immunol. 162, 4576-4588
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Inflammatory Cytokines Provide a Third Signal for Activation of Naive CD4+ and CD8+ T Cells.
J. M. Curtsinger, C. S. Schmidt, A. Mondino, D. C. Lins, R. M. Kedl, M. K. Jenkins, and M. F. Mescher (1999)
J. Immunol. 162, 3256-3262
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Ox-40 Ligand: A Potent Costimulatory Molecule for Sustaining Primary CD4 T Cell Responses.
I. Gramaglia, A. D. Weinberg, M. Lemon, and M. Croft (1998)
J. Immunol. 161, 6510-6517
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Differential Effects of CD28 Engagement and IL-12 on T Cell Activation by Altered Peptide Ligands.
L. Ding and E. M. Shevach (1998)
J. Immunol. 161, 6614-6621
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Human Muscle Cells Express a Functional Costimulatory Molecule Distinct from B7.1 (CD80) and B7.2 (CD86) In Vitro and in Inflammatory Lesions.
L. Behrens, M. Kerschensteiner, T. Misgeld, N. Goebels, H. Wekerle, and R. Hohlfeld (1998)
J. Immunol. 161, 5943-5951
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Specific Suppression of Human CD4+ Th Cell Responses to Pig MHC Antigens by CD8+CD28- Regulatory T Cells.
R. Ciubotariu, A. I. Colovai, G. Pennesi, Z. Liu, D. Smith, P. Berlocco, R. Cortesini, and N. Suciu-Foca (1998)
J. Immunol. 161, 5193-5202
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The Role of the CD40 Pathway in Alloantigen-Induced Hyporesponsiveness In Vivo.
M. Niimi, T. C. Pearson, C. P. Larsen, D. Z. Alexander, D. Hollenbaugh, A. Aruffo, P. S. Linsley, E. Thomas, K. Campbell, W. C. Fanslow, et al. (1998)
J. Immunol. 161, 5331-5337
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Inhibition of NF-kappa B Activation in Combination with Bcl-2 Expression Allows for Persistence of First-Generation Adenovirus Vectors in the Mouse Liver.
A. Lieber, C.-Y. He, L. Meuse, C. Himeda, C. Wilson, and M. A. Kay (1998)
J. Virol. 72, 9267-9277
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CD40 Ligand/Trimer DNA Enhances Both Humoral and Cellular Immune Responses and Induces Protective Immunity to Infectious and Tumor Challenge.
S. Gurunathan, K. R. Irvine, C.-Y. Wu, J. I. Cohen, E. Thomas, C. Prussin, N. P. Restifo, and R. A. Seder (1998)
J. Immunol. 161, 4563-4571
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Mutations of the CD40 Ligand Gene and Its Effect on CD40 Ligand Expression in Patients With X-Linked Hyper IgM Syndrome.
K. Seyama, S. Nonoyama, I. Gangsaas, D. Hollenbaugh, H. F. Pabst, A. Aruffo, and H. D. Ochs (1998)
Blood 92, 2421-2434
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CD40 Ligand-Mediated Interactions Are Involved in the Generation of Memory CD8+ Cytotoxic T Lymphocytes (CTL) but Are Not Required for the Maintenance of CTL Memory following Virus Infection.
P. Borrow, D. F. Tough, D. Eto, A. Tishon, I. S. Grewal, J. Sprent, R. A. Flavell, and M. B. A. Oldstone (1998)
J. Virol. 72, 7440-7449
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Antitumor Effect of CD40 Ligand: Elicitation of Local and Systemic Antitumor Responses by IL-12 and B7.
A. Nakajima, T. Kodama, S. Morimoto, M. Azuma, K. Takeda, H. Oshima, S.-i. Yoshino, H. Yagita, and K. Okumura (1998)
J. Immunol. 161, 1901-1907
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Circumvention of Immunity to the Adenovirus Major Coat Protein Hexon.
S. Roy, P. S. Shirley, A. McClelland, and M. Kaleko (1998)
J. Virol. 72, 6875-6879
   Abstract »    Full Text »    PDF »
Requirements for B7-CD28 Costimulation in Mucosal IgA Responses: Paradoxes Observed in CTLA4-H{gamma}1 Transgenic Mice.
E. Gardby, P. Lane, and N. Y. Lycke (1998)
J. Immunol. 161, 49-59
   Abstract »    Full Text »    PDF »


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