Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease

Yonglian Sun, Helen M. Chen, Sumit K. Subudhi, Jonathan Chen, Rima Koka, Lieping Chen, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

165 Scopus citations


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 languageEnglish (US)
Pages (from-to)1405-1413
Number of pages9
JournalNature medicine
Issue number12
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease'. Together they form a unique fingerprint.

Cite this