Abstract
Vitamin A deficiency leads to increased susceptibility to a spectrum of infectious diseases. The studies presented dissect the intrinsic role of each of the retinoic acid receptor (RAR) isoforms in the clonal expansion, differentiation, and survival of pathogen-specific CD8 T cells in vivo. The data show that RARα is required for the expression of gut-homing receptors on CD8(+) T cells and survival of CD8(+) T cells in vitro. Furthermore, RARα is essential for survival of CD8(+) T cells in vivo following Listeria monocytogenes infection. In contrast, RARβ deletion leads to modest deficiency in Ag-specific CD8(+) T cell expansion during infection. The defective survival of RARα-deficient CD8(+) T cells leads to a deficiency in control of L. monocytogenes expansion in the spleen. To our knowledge, these are the first comparative studies of the role of RAR isoforms in CD8(+) T cell immunity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Proliferation
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Cell Survival / genetics
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Cell Survival / immunology
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Flow Cytometry
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Gene Expression / immunology
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Host-Pathogen Interactions / immunology
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-2 / immunology
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Interleukin-2 / metabolism
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Listeria monocytogenes / immunology*
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Listeria monocytogenes / physiology
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Listeriosis / immunology*
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Listeriosis / microbiology
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Retinoic Acid / deficiency
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / immunology*
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Retinoic Acid Receptor alpha
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Retinoic Acid Receptor gamma
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Reverse Transcriptase Polymerase Chain Reaction
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Spleen / immunology
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Spleen / metabolism
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Spleen / microbiology
Substances
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Interleukin-2
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Rara protein, mouse
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Receptors, Retinoic Acid
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Retinoic Acid Receptor alpha
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retinoic acid receptor beta
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Interferon-gamma