Abstract
Intraepithelial lymphocytes (IEL) of the small murine bowel represent a unique population of mostly CD8(+) T lymphocytes that reside within the epithelial cell layer of the intestinal mucosa. The close interaction with epithelial cells appears to be crucial for IEL survival since isolation and ex vivo culture induces massive apoptosis in this lymphocyte population. Here, we provide evidence that this form of IEL cell death may be mediated at least in part by endogenously produced glucocorticoids since adrenalectomy or treatment of mice with a glucocorticoid receptor antagonist significantly enhanced ex vivo survival of IEL. We further demonstrate that ex vivo activation of IEL induces upregulation of anti-apoptotic gene products, compensates for the lack of survival cytokines and rescues from apoptotic cell death. Thus, similar to thymocytes and T cell hybridomas, IEL survival may be regulated by the antagonistic action of TCR activation and glucocorticoids.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Adrenalectomy
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Animals
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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CD3 Complex / immunology
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CD3 Complex / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / metabolism
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Cell Death* / drug effects
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Cell Survival* / drug effects
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Dexamethasone / pharmacology
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Epithelial Cells / cytology
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Epithelial Cells / immunology
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Fas Ligand Protein
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Glucocorticoids / metabolism
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Inhibitor of Apoptosis Proteins
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Insect Proteins*
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Intestinal Mucosa / cytology
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / immunology*
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Lymphocytes / cytology*
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Lymphocytes / drug effects
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Lymphocytes / metabolism
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Male
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred BALB C
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Proteins*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Receptors, Glucocorticoid / antagonists & inhibitors
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Receptors, Glucocorticoid / metabolism
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Spleen / cytology
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Spleen / immunology
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Tumor Necrosis Factor-alpha / metabolism
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bcl-X Protein
Substances
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Actins
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Bacterial Proteins
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Bcl2l1 protein, mouse
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CD3 Complex
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Fas Ligand Protein
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Fasl protein, mouse
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Glucocorticoids
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Inhibitor of Apoptosis Proteins
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Insect Proteins
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Membrane Glycoproteins
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Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Glucocorticoid
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Tumor Necrosis Factor-alpha
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bcl-X Protein
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Dexamethasone