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 autoim mune disease, including the New Zealand Black (NZB) strain. In particu lar, studies on NZB mice have documented abnormalities in thymic strom al architecture and epithelial cell growth in vitro. These abnormaliti es are indicative of thymic problems which may lead to improper thymoc yte education and immune dysfunction. Neurotropin, an agent with immun omodulating properties has been shown to normalize T-cell activity and a variety of immune functions in (NZB x NZW F1 mice as well as experi mentally induced allergic encephalomyelitis (EAE) in Lewis rats. To fu rther understand the mechanism of action of Neurotropin, its action on the thymic integrity of NZB mice was studied, Neurotropin was adminis tered daily to neonatal NZB mice from days 14 to 27 after birth. A pan el of monoclonal antibodies specific for mouse thymic epithelial and n on-epithelial cell-markers were then used to monitor the effects of Ne urotropin on thymic structure. Comparisons were made to saline-treated NZB control mice. MTS10, a monoclonal antibody (mAb) which stains bot h subcapsular and medullary thymic epithelia, demonstrated striking de fects in control NZB mice. However, Neurotropin treatment increased me dullar cellularity and normalized structural staining patterns of MTS1 0. MTS39, which stains cortical, subcapsular and medullary epithelia, demonstrated an increase in cortical and subcapsular staining followin g 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 cl usters, showed little change in staining pattern. No thymic abnormalit ies were detected in BALB/c mice given either saline or Neurotropin. T hese data suggest that thymic defects consistently associated with mur ine lupus may be partially alleviated through the use of Neurotropin.