International Immunology, Vol 10, 727-741, Copyright © 1998 by Oxford University Press
R Ettinger, R Mebius, JL Browning, SA Michie, S van Tuijl, G Kraal, W van Ewijk and HO McDevitt
Previously, we have reported that neutralization of surface lymphotoxin
(LT-alphabeta) in mice which expressed an LT-beta receptor-Fc fusion
protein, driven by the cytomegalovirus promoter, resulted in an array of
anatomic abnormalities. We now report that mice which express a tumor
necrosis factor (TNF) receptor p60-Fc fusion protein (which neutralizes TNF
and soluble LT-alpha3 activity) develop unique lymphoid abnormalities. Our
data demonstrate that some aspects of peripheral lymphoid organ development
require both surface LT-alphabeta and TNF interacting with their specific
receptors. However, these related cytokines are also capable of signaling
distinct developmental events. Splenic MAdCAM-1 expression, follicular
dendritic cell localization and normal Peyer's patch development all
require both surface LT-alphabeta and TNF activity. Marginal zone formation
and splenic B cell localization primarily require surface
LT-alphabeta-LT-beta receptor interactions. Primary follicle formation was
dependent upon TNF receptor(s) engagement. Interestingly spleen, lymph
nodes and Peyer's patches from TNF receptor p60-Fc-expressing mice all
develop different abnormalities, suggesting distinct pathways of
development in these lymphoid organs. Thymus development appears to be
independent of these signaling pathways. These results demonstrate that TNF
and LT are crucial for normal peripheral, but not central lymphoid organ
development.
ARTICLES
Effects of tumor necrosis factor and lymphotoxin on peripheral lymphoid tissue development
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305-5402, USA.
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