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) |
|---|---|
| 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 -