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Apoptosis of T cells and macrophages in the central nervous system of intact and adrenalectomized Lewis rats during experimental allergic encephalomyelitis.

Abstract：

:The adrenocortical response is central to recovery from experimental allergic encephalomyelitis (EAE) in the Lewis rat, as reflected by the increased severity of the disease in adrenalectomized animals. The protection conferred by glucocorticoids is related to the immunosuppressive effects of the steroid, which may include apoptosis of immunocompetent cells. Here we describe T-cell infiltration and apoptosis in spinal cord lesions of intact (INT) and adrenalectomized (ADX) rats during the course of EAE. The normal disease course (peak clinical score 3) was induced following intra-peritoneal transfer of 4 x 10(7) myelin basic protein (MBP)-sensitized spleen lymphocytes to INT rats. Maximum apoptosis of infiltrating T cells (32%) was evident on day 7 and was associated with the expected increase in circulating corticosterone levels and the onset of disease remission. ADX rats, which have no corticosterone response, administered 4 x 10(7) cells displayed rapid and fatal EAE with only minimal signs of T-cell apoptosis (1.9-3.8%). In order to delay the onset and prolong the disease in ADX rats, a lower cell dose was used. In ADX rats injected with 1 x 10(6) cells, disease onset was comparable to INT 4 x 10(7) rats but disease progression was equally rapid and T-cell apoptosis (1.4-8.5%) was similarly low to that seen in ADX rats given the higher dose of cells. Transfer of the lower number of splenocytes (1 x 10(6) cells) to INT rats resulted in only mild EAE (clinical score 0.5-1) which was reflected both in low T cell apoptosis (1.7-16%) and circulating corticosterone levels. In all treatment groups very few apoptotic macrophages were detected ( < 1% of all macrophages) and no differences between groups were apparent. The results suggest that glucocorticoid-mediated T-cell apoptosis, whether initiated directly or indirectly, may contribute to the recovery phase of EAE in Lewis rats.

journal_name

J Autoimmun

journal_title

Journal of autoimmunity

authors

Smith T,Schmied M,Hewson AK,Lassmann H,Cuzner ML

doi

10.1006/jaut.1996.0020

subject

Has Abstract

pub_date

1996-04-01 00:00:00

pages

167-74

issue

eissn

0896-8411

issn

1095-9157

pii

S0896841196900207

journal_volume

pub_type

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Apoptosis of T cells and macrophages in the central nervous system of intact and adrenalectomized Lewis rats during experimental allergic encephalomyelitis.