EXPRESSION OF COSTIMULATORY MOLECULES B7-1 (CD80), B7-2 (CD86), AND INTERLEUKIN-12 CYTOKINE IN MULTIPLE-SCLEROSIS LESIONS

Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal mode ls, stimulation of these self-reactive T cells in the presence of cost imulatory molecules B7-1 results in T cell-mediated autoimmune disease , whereas B7-2 stimulation generates regulatory autoreactive T cells t hat abrogate disease severity. Thus, reactivation in the brain of myel in-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. W e investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 M S and 10 control cases using semiquantitative reverse transcriptase-po lymerase chain reaction and immunocytochemistry. In four cases, vascul ar CNS infarcts with inflammation were compared with MS plaques from t he same brain. We observed increased expression of B7-1 and interleuki n (IL) 12p40 in acute MS plaques, particularly from early disease case s but not in inflammatory infarcts. B7-1 staining was localized predom inantly to the lymphocytes in perivenular inflammatory cuffs but not t he parenchyma. In contrast, B7-2 was expressed predominantly on macrop hages both in MS lesions of varied time duration and in inflammatory i nfarcts. These findings indicate that an early event in the initiation of MS involves upregulation of B7-1 and IL-12, resulting in condition s that maximally stimulate T cell activation and induction of T helper 1-type immune responses.