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Science 27 September 1996:
Vol. 273. no. 5283, pp. 1864 - 1867
DOI: 10.1126/science.273.5283.1864
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Reports

Requirement for CD40 Ligand in Costimulation Induction, T Cell Activation, and Experimental Allergic Encephalomyelitis

Iqbal S. Grewal, Harald G. Foellmer, Kate D. Grewal, Jianchao Xu, Fridrika Hardardottir, Jody L. Baron, Charles A. Janeway Jr., Richard A. Flavell *

The mechanism of CD40 ligand (CD40L)-mediated in vivo activation of CD4+ T cells was examined by investigation of the development of experimental allergic encephalomyelitis (EAE) in CD40L-deficient mice that carried a transgenic T cell receptor specific for myelin basic protein. These mice failed to develop EAE after priming with antigen, and CD4+ T cells remained quiescent and produced no interferon-gamma (IFN-gamma ). T cells were primed to make IFN-gamma and induce EAE by providing these mice with B7.1+ antigen-presenting cells (APCs). Thus, CD40L is required to induce costimulatory activity on APCs for in vivo activation of CD4+ T cells to produce IFN-gamma and to evoke autoimmunity.

I. S. Grewal, K. D. Grewal, J. Xu, C. A. Janeway Jr., R. A. Flavell, Howard Hughes Medical Institute, and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
H. G. Foellmer, Yale Neurotransplant Program, Yale University School of Medicine, New Haven, CT 06510, USA.
F. Hardardottir and J. L. Baron, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
*   To whom correspondence should be addressed at Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

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J. Immunol. 161, 5943-5951
   Abstract »    Full Text »    PDF »
Neutralizing Antibodies to IFN-{gamma}-Inducing Factor Prevent Experimental Autoimmune Encephalomyelitis.
G. Wildbaum, S. Youssef, N. Grabie, and N. Karin (1998)
J. Immunol. 161, 6368-6374
   Abstract »    Full Text »    PDF »
In Vivo Survival of  Viral Antigen-specific T Cells that Induce Experimental Autoimmune Encephalomyelitis.
R. L. Ufret-Vincenty, L. Quigley, N. Tresser, S. H. Pak, A. Gado, S. Hausmann, K. W. Wucherpfennig, and S. Brocke (1998)
J. Exp. Med. 188, 1725-1738
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Expression of Costimulatory Molecule CD40 in Murine Heart With Acute Myocarditis and Reduction of Inflammation by Treatment With Anti-CD40L/B7-1 Monoclonal Antibodies.
Y. Seko, N. Takahashi, M. Azuma, H. Yagita, K. Okumura, and Y. Yazaki (1998)
Circ. Res. 83, 463-469
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Kinetics of Expression of Costimulatory Molecules and Their Ligands in Murine Relapsing Experimental Autoimmune Encephalomyelitis In Vivo.
S. Issazadeh, V. Navikas, M. Schaub, M. Sayegh, and S. Khoury (1998)
J. Immunol. 161, 1104-1112
   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 »
Presentation of Proteolipid Protein Epitopes and B7-1-Dependent Activation of Encephalitogenic T Cells by IFN-{gamma}-Activated SJL/J Astrocytes.
L. Tan, K. B. Gordon, J. P. Mueller, L. A. Matis, and S. D. Miller (1998)
J. Immunol. 160, 4271-4279
   Abstract »    Full Text »    PDF »
CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive beta -chemokines.
R. S. Kornbluth, K. Kee, and D. D. Richman (1998)
PNAS 95, 5205-5210
   Abstract »    Full Text »    PDF »
CD40 Ligand Is Not Essential for Induction of Type 1 Cytokine Responses or Protective Immunity after Primary or Secondary Infection With Histoplasma capsulatum.
P. Zhou and R. A. Seder (1998)
J. Exp. Med. 187, 1315-1324
   Abstract »    Full Text »    PDF »
Human Mitogen-activated Protein Kinase Kinase 7 (MKK7) Is a Highly Conserved c-Jun N-terminal Kinase/Stress-activated Protein Kinase (JNK/SAPK) Activated by Environmental Stresses and Physiological Stimuli.
I. N. Foltz, R. E. Gerl, J. S. Wieler, M. Luckach, R. A. Salmon, and J. W. Schrader (1998)
J. Biol. Chem. 273, 9344-9351
   Abstract »    Full Text »    PDF »
Detection of CD40 on Human Thyroid Follicular Cells: Analysis of Expression and Function.
R. A. Metcalfe, R. S. McIntosh, F. Marelli-Berg, G. Lombardi, R. Lechler, and A. P. Weetman (1998)
J. Clin. Endocrinol. Metab. 83, 1268-1274
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Cutting Edge: CD40 Ligand Is Not Essential for the Development of Cell-Mediated Immunity and Resistance to Mycobacterium tuberculosis.
A. Campos-Neto, P. Ovendale, T. Bement, T. A. Koppi, W. C. Fanslow, M. A. Rossi, and M. R. Alderson (1998)
J. Immunol. 160, 2037-2041
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CD4+ T Cell Help Impairs CD8+ T Cell Deletion Induced by Cross-presentation of Self-Antigens and Favors Autoimmunity.
C. Kurts, F. R. Carbone, M. Barnden, E. Blanas, J. Allison, W. R. Heath, and J. F.A.P. Miller (1997)
J. Exp. Med. 186, 2057-2062
   Abstract »    Full Text »    PDF »
CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates.
A. D. Kirk, D. M. Harlan, N. N. Armstrong, T. A. Davis, Y. Dong, G. S. Gray, X. Hong, D. Thomas, J. H. Fechner Jr., and S. J. Knechtle (1997)
PNAS 94, 8789-8794
   Abstract »    Full Text »    PDF »
Transient immunomodulation with anti-CD40 ligand antibody and CTLA4Ig enhances persistence and secondary adenovirus-mediated gene transfer into mouse liver.
M. A. Kay, L. Meuse, A. M. Gown, P. Linsley, D. Hollenbaugh, A. Aruffo, H. D. Ochs, and C. B. Wilson (1997)
PNAS 94, 4686-4691
   Abstract »    Full Text »    PDF »
Ligation of CD40 Stimulates the Induction of Nitric-oxide Synthase in Microglial Cells.
M. Jana, X. Liu, S. Koka, S. Ghosh, T. M. Petro, and K. Pahan (2001)
J. Biol. Chem. 276, 44527-44533
   Abstract »    Full Text »    PDF »


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