Influence of neurotropin on thymic microenvironmental abnormalities of NZB mice

Degeneration of thymic epithelial cells as a component of accelerated thymic involution has been noted in mouse models of spontaneous autoimmune disease, including the New Zealand Black (NZB) strain. In particular, studies on NZB mice have documented abnormalities in thymic stromal architecture and epithelial cell growth in vitro. These abnormalities are indicative of thymic problems which may lead to improper thymocyte education and immune dysfunction. Neurotropin, an agent with immunomodulating properties has been shown to normalize T-cell activity and a variety of immune functions in (NZB x NZW) F1 mice as well as experimentally induced allergic encephalomyelitis (EAE) in Lewis rats. To further understand the mechanism of action of Neurotropin, its action on the thymic integrity of NZB mice was studied. Neurotropin was administered daily to neonatal NZB mice from days 14 to 27 after birth. A panel of monoclonal antibodies specific for mouse thymic epithelial and non-epithelial cell-markers were then used to monitor the effects of Neurotropin on thymic structure. Comparisons were made to saline-treated NZB control mice. MTS10, a monoclonal antibody (mAb) which stains both subcapsular and medullary thymic epithelia, demonstrated striking defects in control NZB mice. However, Neurotropin treatment increased medullar cellularity and normalized structural staining patterns of MTS10. MTS39, which stains cortical, subcapsular and medullary epithelia, demonstrated an increase in cortical and subcapsular staining following Neurotropin treatment. Staining with MTS44, a mAb which recognizes a thymic cortical antigen, also showed improved cortical architecture. MTS33, which recognizes cortical thymocytes and medullar epithelial clusters, showed little change in staining pattern. No thymic abnormalities were detected in BALB/c mice given either saline or Neurotropin. These data suggest that thymic defects consistently associated with murine lupus may be partially alleviated through the use of Neurotropin.