|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 187, Number 9, May 4, 1998 1517-1528
By
From the * Centenary Institute of Cancer Medicine and Cell Biology, Sydney, New South Wales 2050, Australia; and Lymphotoxin (LT) is widely regarded as a proinflammatory cytokine with activities equivalent
to tumor necrosis factor (TNF). The contribution of LT to experimental autoimmune encephalomyelitis (EAE) was examined using TNF/LT Department of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia
/ mice, TNF/ mice, and a new LT/
line described here. All mice were generated directly in the C57BL/6 strain and used for the
preparation of radiation bone marrow chimeras to reconstitute peripheral lymphoid organs and restore immunocompetence. This approach overcame the problems related to the lack of
lymph nodes that results from LT gene targeting. We show here that when LT is absent but
TNF is present, EAE progresses normally. In contrast, when TNF is absent but LT is present,
EAE is delayed in onset and inflammatory leukocytes fail to move normally into the central
nervous system parenchyma, even at the peak of disease. In the absence of both cytokines, the
clinical and histological picture is identical to that seen when TNF alone is deficient, including
demyelination. Furthermore, the therapeutic inhibition of TNF and LT with soluble TNF
receptor in unmanipulated wild-type or TNF/ mice exactly reproduces these outcomes. We
conclude from these studies that TNF and LT are functionally distinct cytokines in vivo, and
despite sharing common receptors, show no redundancy of function nor mutual compensation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
