Lymphocyte targeting of the brain in adoptive transfer cryolesion-EAE

Lymphocyte infiltration and microglial activation in experimental autoimmun e encephalomyelitis (EAE) are mainly centred on the spinal cord. However, a cryolesion to one cerebral hemisphere (cryolesion-EAE) induces six-fold en hancement of EAE in the cerebral hemispheres and removal of the cervical ly mph nodes reduces such enhancement by 40 per cent. This study tests the hyp othesis that lymphocytes from donor rats with cryolesion-EAE will selective ly target the brain rather than the spinal cord,when transferred to naive r ecipients. Acute EAE was induced in 15 Lewis rats (donors); ten donors rece ived a cryolesion to the left cerebral hemisphere 8 days post-inoculation o f antigen and adjuvant. Five rats with EAE received no cryolesion. Lymphocy tes from cryolesion-EAE donors or from EAE-only donors were cultured for 72 h in medium containing myelin basic protein and then injected into a total of 21 naive recipients, which were killed 8 days later. The severity of EA E in brains and spinal cords was assessed in immunocytochemically stained s ections by quantifying the number of vessels showing lymphocyte cuffs (W3/1 3 antibody) and the level of MHC class II antigen expression by microglia ( OX6 antibody). When compared with recipients of EAE-only donor lymphocytes, the severity of cerebral EAE was increased 2- to 2.6-fold in the recipient s of crylesion-EAE donor lymphocytes (p<0.01); EAE in the spinal cord mas r educed, These results suggest that lymphocytes from cryolesion-EAE donors p referentially target the brain in recipient animals in preference to the sp inal cord. By analogy with cryolesion-EAE, focal central nervous system (CN S) damage with drainage of auto-antigens to regional lymph nodes in man may play a role in determining the site and timing of initial and recurrent mu ltiple sclerosis lesions. Copyright (C) 1999 John Wiley & Sons, Ltd.