Abstract
Humans and mice deficient in Fas, a tumor necrosis factor (TNF)-receptor family member, cannot induce apoptosis of autoreactive cells, and consequently develop progressive lymphoproliferative disorders and lupus-like autoimmune diseases. Previous studies have shown that short-term administrations of agonistic monoclonal antibodies against CD137, another TNF-receptor family member, activate T cells and induce rejection of allografts and established tumors. Here we report that treatment with an agonistic monoclonal antibody to CD137 (2A) blocks lymphadenopathy and spontaneous autoimmune diseases in Fas-deficient MRL/lpr mice, ultimately leading to their prolonged survival. Notably, 2A treatment rapidly augments IFN-γ production, and induces the depletion of autoreactive B cells and abnormal double-negative T cells, possibly by increasing their apoptosis through Fas- and TNF receptor-independent mechanisms. This study demonstrates that agonistic monoclonal antibodies specific for costimulatory molecules can be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression.
Original language | English (US) |
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Pages (from-to) | 1405-1413 |
Number of pages | 9 |
Journal | Nature Medicine |
Volume | 8 |
Issue number | 12 |
DOIs | |
State | Published - Dec 1 2002 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. / Sun, Yonglian; Chen, Helen M.; Subudhi, Sumit K.; Chen, Jonathan; Koka, Rima; Chen, Lieping; Fu, Yang Xin.
In: Nature Medicine, Vol. 8, No. 12, 01.12.2002, p. 1405-1413.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease
AU - Sun, Yonglian
AU - Chen, Helen M.
AU - Subudhi, Sumit K.
AU - Chen, Jonathan
AU - Koka, Rima
AU - Chen, Lieping
AU - Fu, Yang Xin
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Humans and mice deficient in Fas, a tumor necrosis factor (TNF)-receptor family member, cannot induce apoptosis of autoreactive cells, and consequently develop progressive lymphoproliferative disorders and lupus-like autoimmune diseases. Previous studies have shown that short-term administrations of agonistic monoclonal antibodies against CD137, another TNF-receptor family member, activate T cells and induce rejection of allografts and established tumors. Here we report that treatment with an agonistic monoclonal antibody to CD137 (2A) blocks lymphadenopathy and spontaneous autoimmune diseases in Fas-deficient MRL/lpr mice, ultimately leading to their prolonged survival. Notably, 2A treatment rapidly augments IFN-γ production, and induces the depletion of autoreactive B cells and abnormal double-negative T cells, possibly by increasing their apoptosis through Fas- and TNF receptor-independent mechanisms. This study demonstrates that agonistic monoclonal antibodies specific for costimulatory molecules can be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression.
AB - Humans and mice deficient in Fas, a tumor necrosis factor (TNF)-receptor family member, cannot induce apoptosis of autoreactive cells, and consequently develop progressive lymphoproliferative disorders and lupus-like autoimmune diseases. Previous studies have shown that short-term administrations of agonistic monoclonal antibodies against CD137, another TNF-receptor family member, activate T cells and induce rejection of allografts and established tumors. Here we report that treatment with an agonistic monoclonal antibody to CD137 (2A) blocks lymphadenopathy and spontaneous autoimmune diseases in Fas-deficient MRL/lpr mice, ultimately leading to their prolonged survival. Notably, 2A treatment rapidly augments IFN-γ production, and induces the depletion of autoreactive B cells and abnormal double-negative T cells, possibly by increasing their apoptosis through Fas- and TNF receptor-independent mechanisms. This study demonstrates that agonistic monoclonal antibodies specific for costimulatory molecules can be used as novel therapeutic agents to delete autoreactive lymphocytes and block autoimmune disease progression.
UR - http://www.scopus.com/inward/record.url?scp=0036913169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036913169&partnerID=8YFLogxK
U2 - 10.1038/nm796
DO - 10.1038/nm796
M3 - Article
C2 - 12426559
AN - SCOPUS:0036913169
VL - 8
SP - 1405
EP - 1413
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 12
ER -