Autoantibodies to laminin 1 in brown Norway and Lewis rats: Epitopes, cytokines, and influence of xenobiotics

Laminins are genetically conserved, reflecting their similar functional roles across species. Several diseases have been reported in which patients develop autoantibodies to laminin 1. However the pathogenic role of these autoantibodies is unclear. We have therefore established the following specific aim: To examine the regulation of autoimmune responses to laminin 1 in vivo in different rat strains. We have focused on regulation induced by cytokines produced by APC and responding T cells.^ In an immunization model using BN and LEW rats it was found that differences exist between their immune responses to laminin 1. Both strains made antibodies to mouse laminin 1 in CFA. BN rats however produced an autoimmune response to laminin 1, while LEW rats do not. The BN rat responded to a limited number of peptides of laminin 1, however several isotypes of IgG were present. Treatment with LPS partially inhibited the autoimmune response of BN rats to laminin 1. BN rats produced autoantibodies to laminin 1 when exposed to mercury, but LEW rats did not.^ The response of BN rats appeared type-2-cytokine dependent but reactivity to laminin 1 peptides was broad. The addition of exogenous cytokines had little effect on the isotype of antibodies to laminin 1. Co-administration of antibodies to IL-4 however, enhanced the autoimmune response of BN rats.^ These data suggest that immunization with mouse laminin 1 in CFA results in autoimmune responses to laminin 1 in the BN rat with little cytokine polarization. In mercury-treated BN rats, autoimmune responses also occur to laminin 1, but the cytokine response is strongly polarized. Finally the anti-IL-4 results suggest that anti-cytokine antibodies may protect or potentiate cytokine function in vivo.