|
|
||||||||
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.
This article has been cited by other articles:
![]() |
L. E. Mays, L. H. Vandenberghe, R. Xiao, P. Bell, H.-J. Nam, M. Agbandje-McKenna, and J. M. Wilson Adeno-Associated Virus Capsid Structure Drives CD4-Dependent CD8+ T Cell Response to Vector Encoded Proteins J. Immunol., May 15, 2009; 182(10): 6051 - 6060. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Salek-Ardakani, R. Arens, R. Flynn, A. Sette, S. P. Schoenberger, and M. Croft Preferential Use of B7.2 and Not B7.1 in Priming of Vaccinia Virus-Specific CD8 T Cells J. Immunol., March 1, 2009; 182(5): 2909 - 2918. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Grujic, P. J. Holst, J. P. Christensen, and A. R. Thomsen Fusion of a viral antigen to invariant chain leads to augmented T-cell immunity and improved protection in gene-gun DNA-vaccinated mice J. Gen. Virol., February 1, 2009; 90(2): 414 - 422. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Bartholdy, J. E. Christensen, M. Grujic, J. P. Christensen, and A. R. Thomsen T-cell intrinsic expression of MyD88 is required for sustained expansion of the virus-specific CD8+ T-cell population in LCMV-infected mice J. Gen. Virol., February 1, 2009; 90(2): 423 - 431. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Bonefeld, M. Haks, B. Nielsen, M. von Essen, L. Boding, A. K. Hansen, J. M. Larsen, N. Odum, P. Krimpenfort, A. Kruisbeek, et al. TCR Down-Regulation Controls Virus-Specific CD8+ T Cell Responses J. Immunol., December 1, 2008; 181(11): 7786 - 7799. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Grujic, J. P. Christensen, M. R. Sorensen, M. Abrink, G. Pejler, and A. R. Thomsen Delayed Contraction of the CD8+ T Cell Response toward Lymphocytic Choriomeningitis Virus Infection in Mice Lacking Serglycin J. Immunol., July 15, 2008; 181(2): 1043 - 1051. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. G. H. Hernandez, L. Shen, and K. L. Rock CD40 on APCs Is Needed for Optimal Programming, Maintenance, and Recall of CD8+ T Cell Memory Even in the Absence of CD4+ T Cell Help J. Immunol., April 1, 2008; 180(7): 4382 - 4390. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. D. Elzey, N. W. Schmidt, S. A. Crist, T. P. Kresowik, J. T. Harty, B. Nieswandt, and T. L. Ratliff Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge Blood, April 1, 2008; 111(7): 3684 - 3691. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Fuse, W. Zhang, and E. J. Usherwood Control of Memory CD8+ T Cell Differentiation by CD80/CD86-CD28 Costimulation and Restoration by IL-2 during the Recall Response J. Immunol., January 15, 2008; 180(2): 1148 - 1157. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-P. Raue and M. K. Slifka Pivotal Advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection J. Leukoc. Biol., May 1, 2007; 81(5): 1165 - 1175. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. G. H. Hernandez, L. Shen, and K. L. Rock CD40-CD40 Ligand Interaction between Dendritic Cells and CD8+ T Cells Is Needed to Stimulate Maximal T Cell Responses in the Absence of CD4+ T Cell Help J. Immunol., March 1, 2007; 178(5): 2844 - 2852. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Bartholdy, S. O. Kauffmann, J. P. Christensen, and A. R. Thomsen Agonistic Anti-CD40 Antibody Profoundly Suppresses the Immune Response to Infection with Lymphocytic Choriomeningitis Virus J. Immunol., February 1, 2007; 178(3): 1662 - 1670. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Fuse, J. J. Obar, S. Bellfy, E. K. Leung, W. Zhang, and E. J. Usherwood CD80 and CD86 Control Antiviral CD8+ T-Cell Function and Immune Surveillance of Murine Gammaherpesvirus 68. J. Virol., September 1, 2006; 80(18): 9159 - 9170. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. P. Ciavarra, A. Stephens, S. Nagy, M. Sekellick, and C. Steel Evaluation of Immunological Paradigms in a Virus Model: Are Dendritic Cells Critical for Antiviral Immunity and Viral Clearance? J. Immunol., July 1, 2006; 177(1): 492 - 500. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Honstettre, S. Meghari, J. A. Nunes, H. Lepidi, D. Raoult, D. Olive, and J.-L. Mege Role for the CD28 Molecule in the Control of Coxiella burnetii Infection Infect. Immun., March 1, 2006; 74(3): 1800 - 1808. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. C. Kemball, E. D. H. Lee, E. Szomolanyi-Tsuda, T. C. Pearson, C. P. Larsen, and A. E. Lukacher Costimulation Requirements for Antiviral CD8+ T Cells Differ for Acute and Persistent Phases of Polyoma Virus Infection J. Immunol., February 1, 2006; 176(3): 1814 - 1824. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Song, X. Tang, K. M. Harms, and M. Croft OX40 and Bcl-xL Promote the Persistence of CD8 T Cells to Recall Tumor-Associated Antigen J. Immunol., September 15, 2005; 175(6): 3534 - 3541. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. E. A. T. van Berkel, E. H. R. Schrijver, F. M. A. Hofhuis, A. H. Sharpe, A. J. Coyle, C. P. Broeren, K. Tesselaar, and M. A. Oosterwegel ICOS Contributes to T Cell Expansion in CTLA-4 Deficient Mice J. Immunol., July 1, 2005; 175(1): 182 - 188. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Montfort, H. G. A. Bouwer, C. R. Wagner, and D. J. Hinrichs The Development of Functional CD8 T Cell Memory after Listeria monocytogenes Infection Is Not Dependent on CD40 J. Immunol., September 15, 2004; 173(6): 4084 - 4090. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. N. Kristensen, A. N. Madsen, A. R. Thomsen, and J. P. Christensen Cytokine production by virus-specific CD8+ T cells varies with activation state and localization, but not with TCR avidity J. Gen. Virol., June 1, 2004; 85(6): 1703 - 1712. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. E. Juedes, E. Rodrigo, L. Togher, L. H. Glimcher, and M. G. von Herrath T-bet Controls Autoaggressive CD8 Lymphocyte Responses in Type 1 Diabetes J. Exp. Med., April 19, 2004; 199(8): 1153 - 1162. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Khanolkar, M. J. Fuller, and A. J. Zajac CD4 T Cell-Dependent CD8 T Cell Maturation J. Immunol., March 1, 2004; 172(5): 2834 - 2844. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. P. Christensen, S. O. Kauffmann, and A. R. Thomsen Deficient CD4+ T Cell Priming and Regression of CD8+ T Cell Functionality in Virus-Infected Mice Lacking a Normal B Cell Compartment J. Immunol., November 1, 2003; 171(9): 4733 - 4741. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. O. Andreasen, A. R. Thomsen, V. E. Koteliansky, T. I. Novobrantseva, A. G. Sprague, A. R. de Fougerolles, and J. P. Christensen Expression and Functional Importance of Collagen-Binding Integrins, {alpha}1{beta}1 and {alpha}2{beta}1, on Virus-Activated T Cells J. Immunol., September 15, 2003; 171(6): 2804 - 2811. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Lindow, A. Nansen, C. Bartholdy, A. Stryhn, N. J. V. Hansen, T. P. Boesen, T. N. C. Wells, T. W. Schwartz, and A. R. Thomsen The Virus-Encoded Chemokine vMIP-II Inhibits Virus-Induced Tc1-Driven Inflammation J. Virol., July 1, 2003; 77(13): 7393 - 7400. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Giuliani, C. G. Goodyer, J. P. Antel, and V. W. Yong Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity J. Immunol., July 1, 2003; 171(1): 368 - 379. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Triki, M. R. Barbouche, O. Bahri, M. Bejaoui, and K. Dellagi Community-Acquired Poliovirus Infection in Children with Primary Immunodeficiencies in Tunisia J. Clin. Microbiol., March 1, 2003; 41(3): 1203 - 1211. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-L. Wang, Y.-T. Wu, C.-A. Liu, M.-W. Lin, C.-J. Lee, L.-T. Huang, and K. D. Yang Expression of CD40 Ligand on CD4+ T-Cells and Platelets Correlated to the Coronary Artery Lesion and Disease Progress in Kawasaki Disease Pediatrics, February 1, 2003; 111(2): e140 - 147. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Williams, T. M. Onami, A. B. Adams, M. M. Durham, T. C. Pearson, R. Ahmed, and C. P. Larsen Cutting Edge: Persistent Viral Infection Prevents Tolerance Induction and Escapes Immune Control Following CD28/CD40 Blockade-Based Regimen J. Immunol., November 15, 2002; 169(10): 5387 - 5391. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-M. Hu, H. Winter, J. Ma, M. Croft, W. J. Urba, and B. A. Fox CD28, TNF Receptor, and IL-12 Are Critical for CD4-Independent Cross-Priming of Therapeutic Antitumor CD8+ T Cells J. Immunol., November 1, 2002; 169(9): 4897 - 4904. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. N. Kristensen, J. P. Christensen, and A. R. Thomsen High numbers of IL-2-producing CD8+ T cells during viral infection: correlation with stable memory development J. Gen. Virol., September 1, 2002; 83(9): 2123 - 2133. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
M. J. Ekkens, Z. Liu, Q. Liu, A. Foster, J. Whitmire, J. Pesce, A. H. Sharpe, J. F. Urban, and W. C. Gause Memory Th2 Effector Cells Can Develop in the Absence of B7-1/B7-2, CD28 Interactions, and Effector Th Cells After Priming with an Intestinal Nematode Parasite J. Immunol., June 15, 2002; 168(12): 6344 - 6351. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
I.-J. Kim, E. Flano, D. L. Woodland, and M. A. Blackman Antibody-Mediated Control of Persistent {gamma}-Herpesvirus Infection J. Immunol., April 15, 2002; 168(8): 3958 - 3964. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nansen, J. P. Christensen, S. O. Andreasen, C. Bartholdy, J. E. Christensen, and A. R. Thomsen The role of CC chemokine receptor 5 in antiviral immunity Blood, February 15, 2002; 99(4): 1237 - 1245. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. L. Compton and J. P. Farrell CD28 Costimulation and Parasite Dose Combine to Influence the Susceptibility of BALB/c Mice to Infection with Leishmania major J. Immunol., February 1, 2002; 168(3): 1302 - 1308. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. V. Serbina, V. Lazarevic, and J. L. Flynn CD4+ T Cells Are Required for the Development of Cytotoxic CD8+ T Cells During Mycobacterium tuberculosis Infection J. Immunol., December 15, 2001; 167(12): 6991 - 7000. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |