Y. Kanamaru et al., Blockade of TGF-beta signaling in T cells prevents the development of experimental glomerulonephritis, J IMMUNOL, 166(4), 2001, pp. 2818-2823
Anti-glomerular basement membrane (GBM) Ab-induced glomerulonephritis (GN)
at late stage is thought to be mediated by T cells. However, signaling path
ways of T cells that are involved in the development of anti-GEM Ab-induced
GN are unclear, We have recently established transgenic mice expressing Sm
ad7, an inhibitor of TGF-beta signaling, in mature T cells, where signaling
by TGP-beta was blocked specifically in T cells. In this study, we showed
that anti-GEM Ab-induced GN was suppressed in several measures in the trans
genic mice including the severity; of glomerular changes, proteinuria, rena
l function, and; CD4 T cell infiltration into the glomeruli without down-re
gulation of CD62 ligand (CD62L) (L-selectin) expression on CD4 T cells. Fur
thermore, treatment,vith the soluble fusion protein of CD62L and IgG enhanc
ed anti-GEM Ah-induced GN, These findings indicated that blockade of TGF-be
ta signaling in T cells prevented the development of anti-GEM Ah-induced GN
, Because CD62L on T cells appears to be inhibitory for the development of
anti-GEM Ah-induced GN, persistent expression of CD62L on CD4 T cells may e
xplain, at least in part, the suppression of anti-GEM Ab-induced GN in the
transgenic mice. Our findings suggest that the development of anti-GEM Ab-i
nduced GN requires TGF-beta /Smad signaling in T cells.