TY - JOUR
T1 - Critical involvement of OX40 ligand signals in the T cell priming events during experimental autoimmune encephalomyelitis
AU - Ndhlovu, L. C.
AU - Ishii, N.
AU - Murata, K.
AU - Sato, T.
AU - Sugamura, K.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2001/9/1
Y1 - 2001/9/1
N2 - OX40 ligand (OX40L) expressed on APCs, and its receptor, OX40 present on activated T cells, are members of the TNF/TNFR family, respectively, and have been located at the sites of inflammatory conditions. We have observed in OX40L-deficient mice (OX40L-/-) an impaired APC capacity and in our recently constructed transgenic mice expressing OX40L (OX40L-Tg), a markedly enhanced T cell response to protein Ags. Using these mice, we demonstrate here the critical involvement of the OX40L-OX40 interaction during the T cell priming events in the occurrence of experimental autoimmune encephalomyelitis (EAE). In OX40L-/- mice, abortive T cell priming greatly reduced the clinical manifestations of actively induced EAE, coupled with a reduction in IFN-γ, IL-2, and IL-6 production in vitro. Adoptive transfer experiments however revealed an efficient transfer of disease to OX40L-/- mice using wild-type donor T cells, indicating an intact capacity of OX40L-/- mice to initiate effector responses. On the other hand, OX40L-/- donor T cells failed to transfer disease to wild-type recipient mice. Furthermore, OX40L-Tg mice developed a greater severity of EAE despite a delayed onset, while both OX40L-Tg/CD28-/- and OX40L-Tg/CD40-/- mice failed to develop EAE demonstrating a requisite for these molecules. These findings indicate a pivotal role played by OX40L in the pathogenesis of EAE.
AB - OX40 ligand (OX40L) expressed on APCs, and its receptor, OX40 present on activated T cells, are members of the TNF/TNFR family, respectively, and have been located at the sites of inflammatory conditions. We have observed in OX40L-deficient mice (OX40L-/-) an impaired APC capacity and in our recently constructed transgenic mice expressing OX40L (OX40L-Tg), a markedly enhanced T cell response to protein Ags. Using these mice, we demonstrate here the critical involvement of the OX40L-OX40 interaction during the T cell priming events in the occurrence of experimental autoimmune encephalomyelitis (EAE). In OX40L-/- mice, abortive T cell priming greatly reduced the clinical manifestations of actively induced EAE, coupled with a reduction in IFN-γ, IL-2, and IL-6 production in vitro. Adoptive transfer experiments however revealed an efficient transfer of disease to OX40L-/- mice using wild-type donor T cells, indicating an intact capacity of OX40L-/- mice to initiate effector responses. On the other hand, OX40L-/- donor T cells failed to transfer disease to wild-type recipient mice. Furthermore, OX40L-Tg mice developed a greater severity of EAE despite a delayed onset, while both OX40L-Tg/CD28-/- and OX40L-Tg/CD40-/- mice failed to develop EAE demonstrating a requisite for these molecules. These findings indicate a pivotal role played by OX40L in the pathogenesis of EAE.
UR - http://www.scopus.com/inward/record.url?scp=0035451519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035451519&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.167.5.2991
DO - 10.4049/jimmunol.167.5.2991
M3 - Article
C2 - 11509650
AN - SCOPUS:0035451519
VL - 167
SP - 2991
EP - 2999
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 5
ER -