title: Repeated stress suppresses interferon-gamma production by murine intestinal intraepithelial lymphocytes.
abstract: Intestinal intraepithelial lymphocytes (IEL), one of the major effector components in the mucosal immune system, are phenotypically and functionally distinct from thymic and peripheral T cells. To investigate the effect of repeated stress on the number and function of IEL, we exposed male C3H/HeN mice to mild electric foot shock for 30 min/day for 5 consecutive days. Immediately after the final foot shock stress, the blood, spleen, thymus and small intestine of each of the mice were obtained. As a functional measure, we evaluated interferon (IFN)- gamma production by IEL, since IFN-gamma is a key immunomodulating cytokine in mucosal immune responses. Serum corticosterone level was elevated immediately after foot shock stress. There were no significant changes in the number of whole IEL and CD3+ IEL subsets after the stress. In contrast, the stress led to a significant decrease in the total number of thymocytes, particularly the reduction in the number of CD4+CD8+ thymocytes. Thymocytes expressed the highest level of intracellular glucocorticoid receptor (GR), followed by splenocytes and IEL. The foot shock stress induced a marked suppression of IFN-gamma production by IEL, when stimulated with immobilized anti-CD3 monoclonal antibody. Furthermore, corticosterone suppressed the IFN-gamma production by cultured IEL, which was prevented by Mifepristone (RU486), a GR antagonist. In summary, repeated foot shock stress did not alter the numbers of IEL and CD3+ IEL subsets, but suppressed IFN-gamma production by IEL, which was probably mediated by the elevated corticosterone. We therefore propose that stress influences host defense by suppressing the production of IFN-gamma in IEL.
authors.affiliation: Department of Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai, Japan. xmzhang@mail.tains.tohoku.ac.jp
authors.forename: Xiumin
authors.initials: X
authors.lastname: Zhang
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Okutsu
authors.forename: Osamu
authors.initials: O
authors.lastname: Kanemi
authors.forename: Bahiru
authors.initials: B
authors.lastname: Gametchu
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagatomi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002462:Cell Membrane / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D004597:Electroshock; D004847:Epithelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015735:Mifepristone / Q000494:pharmacology; D010641:Phenotype; D011863:Radioimmunoassay; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D007371:Interferon-gamma; D003345:Corticosterone