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*
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322;
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520; and
Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322
This study documents a striking dichotomy between CD4 and CD8 T
cells in terms of their requirements for CD40-CD40 ligand (CD40L)
costimulation. CD40L-deficient (-/-) mice made potent virus-specific
CD8 T cell responses to dominant as well as subdominant epitopes
following infection with lymphocytic choriomeningitis virus. In
contrast, in the very same mice, virus-specific CD4 T cell responses
were severely compromised. There were 10-fold fewer virus-specific CD4
T cells in CD40L-/- mice compared with those in
CD40L+/+ mice, and this inhibition was seen for both Th1
(IFN-
, IL-2) and Th2 (IL-4) responses. An in vivo functional
consequence of this Th cell defect was the inability of
CD40L-/- mice to control a chronic lymphocytic
choriomeningitis virus infection. This study highlights the importance
of CD40-CD40L interactions in generating virus-specific CD4 T cell
responses and in resolving chronic viral
infection.
This article has been cited by other articles:
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A. D. H. Doody, J. T. Kovalchin, M. A. Mihalyo, A. T. Hagymasi, C. G. Drake, and A. J. Adler Glycoprotein 96 Can Chaperone Both MHC Class I- and Class II-Restricted Epitopes for In Vivo Presentation, but Selectively Primes CD8+ T Cell Effector Function J. Immunol., May 15, 2004; 172(10): 6087 - 6092. [Abstract] [Full Text] [PDF]
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J. C. Sun and M. J. Bevan Cutting Edge: Long-Lived CD8 Memory and Protective Immunity in the Absence of CD40 Expression on CD8 T Cells J. Immunol., March 15, 2004; 172(6): 3385 - 3389. [Abstract] [Full Text] [PDF]
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B. Samten, B. Wizel, H. Shams, S. E. Weis, P. Klucar, S. Wu, R. Vankayalapati, E. K. Thomas, S. Okada, A. M. Krensky, et al. CD40 Ligand Trimer Enhances the Response of CD8+ T Cells to Mycobacterium tuberculosis J. Immunol., March 15, 2003; 170(6): 3180 - 3186. [Abstract] [Full Text] [PDF]
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M. Suresh, H. Molina, M. S. Salvato, D. Mastellos, J. D. Lambris, and M. Sandor Complement Component 3 Is Required for Optimal Expansion of CD8 T Cells During a Systemic Viral Infection J. Immunol., January 15, 2003; 170(2): 788 - 794. [Abstract] [Full Text] [PDF]
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 J. D. Ahlers, I. M. Belyakov, M. Terabe, R. Koka, D. D. Donaldson, E. K. Thomas, and J. A. Berzofsky A push-pull approach to maximize vaccine efficacy: Abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L PNAS, October 1, 2002; 99(20): 13020 - 13025. [Abstract] [Full Text] [PDF]
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 C. Bourgeois, B. Rocha, and C. Tanchot A Role for CD40 Expression on CD8+ T Cells in the Generation of CD8+ T Cell Memory Science, September 20, 2002; 297(5589): 2060 - 2063. [Abstract] [Full Text] [PDF]
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H. Wedemeyer, X.-S. He, M. Nascimbeni, A. R. Davis, H. B. Greenberg, J. H. Hoofnagle, T. J. Liang, H. Alter, and B. Rehermann Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection J. Immunol., September 15, 2002; 169(6): 3447 - 3458. [Abstract] [Full Text] [PDF]
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 J. E. Christensen, J. P. Christensen, N. N. Kristensen, N. J. V. Hansen, A. Stryhn, and A. R. Thomsen Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells Int. Immunol., July 1, 2002; 14(7): 701 - 711. [Abstract] [Full Text] [PDF]
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G. Demirci, W. Gao, X. X. Zheng, T. R. Malek, T. B. Strom, and X. C. Li On CD28/CD40 Ligand Costimulation, Common {gamma}-Chain Signals, and the Alloimmune Response J. Immunol., May 1, 2002; 168(9): 4382 - 4390. [Abstract] [Full Text] [PDF]
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A. L. Marzo, V. Vezys, K. Williams, D. F. Tough, and L. Lefrancois Tissue-Level Regulation of Th1 and Th2 Primary and Memory CD4 T Cells in Response to Listeria Infection J. Immunol., May 1, 2002; 168(9): 4504 - 4510. [Abstract] [Full Text] [PDF]
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D. Montagna, R. Maccario, F. Locatelli, V. Rosti, Y. Yang, P. Farness, A. Moretta, P. Comoli, E. Montini, and A. Vitiello Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy Blood, December 1, 2001; 98(12): 3359 - 3366. [Abstract] [Full Text] [PDF]
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M. Suresh, J. K. Whitmire, L. E. Harrington, C. P. Larsen, T. C. Pearson, J. D. Altman, and R. Ahmed Role of CD28-B7 Interactions in Generation and Maintenance of CD8 T Cell Memory J. Immunol., November 15, 2001; 167(10): 5565 - 5573. [Abstract] [Full Text] [PDF]
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S. E. Hamilton, A. R. Tvinnereim, and J. T. Harty Listeria monocytogenes Infection Overcomes the Requirement for CD40 Ligand in Exogenous Antigen Presentation to CD8+ T Cells J. Immunol., November 15, 2001; 167(10): 5603 - 5609. [Abstract] [Full Text] [PDF]
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M. A. Williams, J. T. Tan, A. B. Adams, M. M. Durham, N. Shirasugi, J. K. Whitmire, L. E. Harrington, R. Ahmed, T. C. Pearson, and C. P. Larsen Characterization of Virus-Mediated Inhibition of Mixed Chimerism and Allospecific Tolerance J. Immunol., November 1, 2001; 167(9): 4987 - 4995. [Abstract] [Full Text] [PDF]
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R. Xiang, F. J. Primus, J. M. Ruehlmann, A. G. Niethammer, S. Silletti, H. N. Lode, C. S. Dolman, S. D. Gillies, and R. A. Reisfeld A Dual-Function DNA Vaccine Encoding Carcinoembryonic Antigen and CD40 Ligand Trimer Induces T Cell-Mediated Protective Immunity Against Colon Cancer in Carcinoembryonic Antigen-Transgenic Mice J. Immunol., October 15, 2001; 167(8): 4560 - 4565. [Abstract] [Full Text] [PDF]
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J. D. Ahlers, I. M. Belyakov, S. Matsui, and J. A. Berzofsky Mechanisms of cytokine synergy essential for vaccine protection against viral challenge Int. Immunol., July 1, 2001; 13(7): 897 - 908. [Abstract] [Full Text] [PDF]
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S. M. Ensminger, B. M. Spriewald, H. V. Sorensen, O. Witzke, E. G. Flashman, A. Bushell, P. J. Morris, M. L. Rose, A. Rahemtulla, and K. J. Wood Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation J. Immunol., July 1, 2001; 167(1): 532 - 541. [Abstract] [Full Text] [PDF]
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 Y. Qian, F. Boisgerault, G. Benichou, and M. R. Dana Blockade of CD40-CD154 Costimulatory Pathway Promotes Survival of Allogeneic Corneal Transplants Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 987 - 994. [Abstract] [Full Text]
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D. Masopust, J. Jiang, H. Shen, and L. Lefrancois Direct Analysis of the Dynamics of the Intestinal Mucosa CD8 T Cell Response to Systemic Virus Infection J. Immunol., February 15, 2001; 166(4): 2348 - 2356. [Abstract] [Full Text] [PDF]
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K. H. Edelmann and C. B. Wilson Role of CD28/CD80-86 and CD40/CD154 Costimulatory Interactions in Host Defense to Primary Herpes Simplex Virus Infection J. Virol., January 15, 2001; 75(2): 612 - 621. [Abstract] [Full Text]
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M. A. Williams, J. Trambley, J. Ha, A. B. Adams, M. M. Durham, P. Rees, S. R. Cowan, T. C. Pearson, and C. P. Larsen Genetic Characterization of Strain Differences in the Ability to Mediate CD40/CD28-Independent Rejection of Skin Allografts J. Immunol., December 15, 2000; 165(12): 6849 - 6857. [Abstract] [Full Text] [PDF]
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 R. S. Kornbluth The emerging role of CD40 ligand in HIV infection J. Leukoc. Biol., September 1, 2000; 68(3): 373 - 382. [Abstract] [Full Text] [PDF]
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 Y. Wan, J. Bramson, A. Pilon, Q. Zhu, and J. Gauldie Genetically Modified Dendritic Cells Prime Autoreactive T Cells through a Pathway Independent of CD40L and Interleukin 12: Implications for Cancer Vaccines Cancer Res., June 1, 2000; 60(12): 3247 - 3253. [Abstract] [Full Text]
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J. T. Tan, J. K. Whitmire, K. Murali-Krishna, R. Ahmed, J. D. Altman, R. S. Mittler, A. Sette, T. C. Pearson, and C. P. Larsen 4-1BB Costimulation Is Required for Protective Anti-Viral Immunity After Peptide Vaccination J. Immunol., March 1, 2000; 164(5): 2320 - 2325. [Abstract] [Full Text] [PDF]
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J. T. Tan, J. K. Whitmire, R. Ahmed, T. C. Pearson, and C. P. Larsen 4-1BB Ligand, a Member of the TNF Family, Is Important for the Generation of Antiviral CD8 T Cell Responses J. Immunol., November 1, 1999; 163(9): 4859 - 4868. [Abstract] [Full Text] [PDF]
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