T-CELL RESPONSES TO MYELIN BASIC-PROTEIN IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS-RESISTANT BALB C MICE/

In strains of mice that are susceptible to experimental autoimmune enc ephalomyelitis (EAE), cloned CD4+ T cells reactive with autologous mye lin basic protein (MBP) have been shown to cause disease when transfer red to naive syngeneic recipients. Recent reports indicate that under particular experimental conditions, 'resistant' strains of mice can al so develop EAE, although cloned cells have not been isolated and chara cterized. An analysis of the characteristics of a panel of MBP-specifi c T cells and the antigen presenting capability of CNS-derived cells o btained from the resistant strain BALB/c is presented here. The data d emonstrate that immunization of EAE-resistant BALB/c mice results in t he activation of a heterogeneous group of T cells reactive with autolo gous MBP. Both peripheral antigen presenting cells, as well as microgl ia isolated from brains of BALB/c mice, are capable of stimulating the se cloned MBP-specific T cells to proliferate. When optimally activate d in vitro and then injected in vivo into syngeneic BALB/c recipients, three clones studied induced severe cachexia, resulting in loss of up to 35% of body weight before death. Two of the clones also induced cl inical and histological EAE, while the third induced only occasional h istological evidence of disease. Differences in epitope recognition, T cell receptor usage, cytokine profiles or regulatory mechanisms of se lf tolerance, may play important roles in preventing potentially destr uctive autoimmune reactions by these T cells capable of recognizing au tologous myelin in the central nervous system.