Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / virology
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CD40 Antigens / metabolism
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CD40 Antigens / physiology*
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CD40 Ligand
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / virology
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Chronic Disease
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Clone Cells
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Drug Synergism
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Epitopes, T-Lymphocyte / analysis
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Ligands
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Lymphocyte Activation / genetics
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Lymphocytic Choriomeningitis / immunology
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Lymphocytic Choriomeningitis / prevention & control*
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Lymphocytic Choriomeningitis / virology
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Lymphocytic choriomeningitis virus / immunology*
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
Substances
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CD40 Antigens
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Epitopes, T-Lymphocyte
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Ligands
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Membrane Glycoproteins
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CD40 Ligand