Y. Takeoka et al., INFLUENCE OF NEUROTROPIN ON THYMIC MICROENVIRONMENTAL ABNORMALITIES OF NZB MICE, International journal of immunotherapy, 11(2), 1995, pp. 49-56
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.