Lethal effect of CD3-specific antibody in mice deficient in TGF-β1 by uncontrolled flu-like syndrome

Sylvain Perruche, Pin Zhang, Takashi Maruyama, Jeffrey A. Bluestone, Philippe Saas, Wan Jun Chen

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

CD3-specific Ab therapy results in a transient, self-limiting, cytokine-associated, flu-like syndrome in experimental animals and in patients, but the underlying mechanism for this spontaneous resolution remains elusive. By using an in vivo model of CD3-specific Ab-induced flu-like syndrome, we show in this paper that a single injection of sublethal dose of the Ab killed all TGF-β1-/- mice. The death of TGF-β1-/- mice was associated with occurrence of this uncontrolled flu-like syndrome, as demonstrated by a sustained storm of systemic inflammatory TNF and IFN-γ cytokines. We present evidence that deficiency of professional phagocytes to produce TGF-β1 after apoptotic T cell clearance may be responsible, together with hypersensitivity of T cells to both activation and apoptosis, for the uncontrolled inflammation. These findings indicate a key role for TGF-β1 and phagocytes in protecting the recipients from lethal inflammation and resolving the flu-like syndrome after CD3-specific Ab treatment. The study may also provide a novel molecular mechanism explaining the early death in TGF-β1-/- mice.

Original languageEnglish
Pages (from-to)953-961
Number of pages9
JournalJournal of Immunology
Volume183
Issue number2
DOIs
Publication statusPublished - 2009 Jul 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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