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

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 4x10(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 4x10(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 1x10(6) cells, disease onset was comparable to INT 4x10(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 (1x10(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. (C) 1996 Academic Press Limited