Regulation of cell death and survival in intestinal intraepithelial lymphocytes.
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.
Brunner
T
T
Division of Immunopathology, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010 Bern, Switzerland. tbrunner@pathology.unibe.ch
Arnold
D
D
Wasem
C
C
Herren
S
S
Frutschi
C
C
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D053222:Fas Ligand Protein; D005938:Glucocorticoids / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051020:bcl-X Protein
D000199:Actins; D001426:Bacterial Proteins; C494812:Bcl2l1 protein, mouse; D017252:CD3 Complex; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D005938:Glucocorticoids; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D003907:Dexamethasone