Induced Minor Malformations in the Neocortex of Normal Mice do not Alter Immunological Functions

Abstract

The interactive relationship between the CNS and the immune system is well established. Major lesions in the brain have been shown to affect immune response. However, whether minor, focal lesions (ectopias), as seen in autoimmune mice, may induce alterations in the immune system is unknown. To address this point, ectopic lesions in the neocortex were induced in neonatal DBA/2 mice (Induced minor malformations; IMM) and their immune capabilities were assessed at adulthood. Serum was collected from each animal and analyzed for the presence of autoantibodies. In addition, splenic lymphocytes and thymocytes were collected to ascertain proliferative capabilities and to assess for possible phenotypic changes in lymphocyte subsets. Mice with IMM did not manifest IgG autoantibodies against cardiolipin, dsDNA or brain membrane antigens. Total lymphocyte cellularity was not affected. The induction of cerebrocortical ectopias did not impair the ability of splenic and thymic lymphocytes to proliferate in response to anti-CD3 antibodies or Concanavalin-A (Con-A) as determined by non-radioactive (Alamar Blue) and radioactive (3H-thymidine) assays. Moreover, no difference in proliferation of instimulated and anti-CD3-stimulated splenic lymphocytes exposed to rIL-2 or rIL-7 was observed. Flow cytometric analysis of a variety of cell surface antigens, indicated that there was no difference in lymphocyte subsets between control and IMM groups. Therefore, we conclude that induced IMM lesions in the CNS of normal DBA/2 mice lo not alter immune functions.