Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 2, Pages 953-961Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0804076
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Funding
- National Institutes of Health, National Institute of Dental and Craniofacial Research
- Institut National du Cancer [PL098]
- Association de Recherche contre le Cancer [3851]
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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-beta 1(-/-) Mice. The death of TGF-beta 1(-/-) mice was associated with occurrence of this uncontrolled flu-like syndrome, as demonstrated by a sustained storm of systemic inflammatory TNF and IFN-gamma cytokines. We present evidence that deficiency of professional phagocytes to produce TGF-beta 1 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-beta 1 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-beta 1(-/-) mice. The Journal of Immunology, 2009, 183: 953-961.
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