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Institute of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark
The primary aim of this report was to evaluate the immune responses of CD40 ligand-deficient (CD40L-/-) mice infected with two viruses known to differ markedly in their capacity to replicate in the host. Lymphocytic choriomeningitis virus (LCMV) is a natural mouse pathogen that replicates widely and extensively, whereas vesicular stomatitis virus (VSV) spreads poorly. We found that the primary response of CD40L-/- mice toward VSV is significantly impaired; proliferation of both CD4+ and CD8+ cells is reduced 2- to 3-fold, few CD8+ cells acquire an activated phenotype, and little functional activity is induced. Very similar results were obtained in VSV-infected, CD28-deficient mice. In contrast, neither CD40L nor CD28 was required for induction of a primary CD8+ response toward LCMV. Surprisingly, lack of CD4+ T cells had no impact on the primary immune response toward any of the viruses, even though the CD40 ligand dependence demonstrated for VSV would be expected to be associated with CD4 dependence. Upon coinfection of VSV-infected mice with LCMV, the requirement for CD40 ligand (but not CD28) could be partially bypassed, as evidenced by a 3-fold increase in the frequency of VSV-specific CD8+ T cells on day 6 postinfection. Finally, despite the fact that the primary LCMV-specific CD8+ response is virtually unimpaired in CD40L-/- mice, their capacity to maintain CD8+ effector activity and to permanently control the infection is significantly reduced. Thus, our results demonstrate that the importance of CD40/CD40L interaction for activation of CD8+ T cells varies between viruses and over time.
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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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H.-W. Mittrucker, M. Kursar, A. Kohler, R. Hurwitz, and S. H. E. Kaufmann Role of CD28 for the Generation and Expansion of Antigen-Specific CD8+ T Lymphocytes During Infection with Listeria monocytogenes J. Immunol., November 15, 2001; 167(10): 5620 - 5627. [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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J. E. Christensen, S. O. Andreasen, J. P. Christensen, and A. R. Thomsen CD11b expression as a marker to distinguish between recently activated effector CD8+ T cells and memory cells Int. Immunol., April 1, 2001; 13(4): 593 - 600. [Abstract] [Full Text] [PDF]
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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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N. Arbour, D. Naniche, D. Homann, R. J. Davis, R. A. Flavell, and M. B.A. Oldstone c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell-mediated Antiviral Immunity J. Exp. Med., March 25, 2002; 195(7): 801 - 810. [Abstract] [Full Text] [PDF]
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