Autoimmunity in New Zealand mice has a genetic and immune basis; however, expression of severity can be modified by viral and other environmental factors as well as sex hormones. The immune factors are complex. These include excessive B-cell activation and abnormal T cell function. A single gene, xid, prevents disease in congenic NZB and (NZB x NZW) Fl and BXSB mice, and markedly retards disease in MRL-lpr/lpr mice. BXSB mice have a Y chromosome-linked gene which accelerates autoimmunity in autoimmune mice, but does not cause it in non-autoimmune mice. This gene requires an autosomal gene from BSXB mice for full expression in NZB mice, but not in NZW mice. All of the autoimune strains studied have a defect in experimental tolerance. In NZB mice, the defect maps to a pre-T stem cell. Small numbers of NZB T-cells interfere with the development of tolerance suggesting that they secrete a factor which causes lymphocyte activation rather than supression. Analysis of cytokines produced by autoimmune mice has led to a first level of appreciation of the importance of low molecular weight mediators of cellular communication in the immune abnormalities of autoimmune mice. The defects in autoimmune mice can be mimicked in normal mice by appropriate manipulation (removal of regulatory T cell function and chronic immune stimulation). Studies of gastrointestinal immunity reveal that ingestion of certain food my fail to induce tolerance normally or even induce an immune response. Therefore, food in the diet of certain patients could trigger immune responses. Different autoimmune mice have increased expression of different oncogenes. lpr/lpr and gld/gld mice have increased myb and T cell receptor (Beta gene). The xid gene prevents increased myc and ras expression, suggesting that that oncogene is associated with the Lyb 5 plus subset and autoantibody production. The studies of gene expression in lpr/lpr mice have pointed to a new pathway for T cell maturation.
