APOPTOSIS OF T-CELLS AND MACROPHAGES IN THE CENTRAL-NERVOUS-SYSTEM OFINTACT AND ADRENALECTOMIZED LEWIS RATS DURING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

The adrenocortical response is central to recovery from experimental a llergic encephalomyelitis (EAE) in the Lewis rat, as reflected by the increased severity of the disease in adrenalectomized animals. The pro tection conferred by glucocorticoids is related to the immunosuppressi ve effects of the steroid, which may include apoptosis of immunocompet ent cells. Here we describe T-cell infiltration and apoptosis in spina l cord lesions of intact (INT) and adrenalectomized (ADX) rats during the course of EAE. The normal disease course (peak clinical score 3) w as induced following intra-peritoneal transfer of 4x10(7) myelin basic protein (MBP)-sensitized spleen lymphocytes to INT rats. Maximum apop tosis of infiltrating T cells (32%) was evident on day 7 and was assoc iated with the expected increase in circulating corticosterone levels and the onset of disease remission. ADX rats, which have no corticoste rone response, administered 4x10(7) cells displayed rapid and fatal EA E 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 rap id and T-cell apoptosis (1.4-8.5%) was similarly low to that seen in A DX rats given the higher dose of cells. Transfer of the lower number o f splenocytes (1x10(6) cells) to INT rats resulted in only mild EAE (c linical score 0.5-1) which was reflected both in low T cell apoptosis (1.7-16%) and circulating corticosterone levels. In all treatment grou ps very few apoptotic macrophages were detected (<1% of all macrophage s) and no differences between groups were apparent. The results sugges t that glucocorticoid-mediated T-cell apoptosis, whether initiated dir ectly or indirectly, may contribute to the recovery phase of EAE in Le wis rats. (C) 1996 Academic Press Limited