CD40-CD40 Ligand Costimulation Is Required for Generating Antiviral CD4 T Cell Responses But Is Dispensable for CD8 T Cell Responses

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-09, Vol.163 (6), p.3194-3201
Main Authors: Whitmire, Jason K, Flavell, Richard A, Grewal, Iqbal S, Larsen, Christian P, Pearson, Thomas C, Ahmed, Rafi
Format: Article
Language:English
Subjects:
Animals
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
CD40 Antigens - metabolism
CD40 Antigens - physiology
CD40 Ligand
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - virology
Chronic Disease
Clone Cells
Drug Synergism
Epitopes, T-Lymphocyte - analysis
Ligands
Lymphocyte Activation - genetics
Lymphocytic Choriomeningitis - immunology
Lymphocytic Choriomeningitis - prevention & control
Lymphocytic Choriomeningitis - virology
Lymphocytic choriomeningitis virus
Lymphocytic choriomeningitis virus - immunology
Membrane Glycoproteins - deficiency
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane Glycoproteins - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
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Summary: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-gamma, 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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.163.6.3194