HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: jimmunol.0804076v1 183/2/953    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Perruche, S. Articles by Chen, W. PubMed PubMed Citation Articles by Perruche, S. Articles by Chen, W. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH

Lethal Effect of CD3-Specific Antibody in Mice Deficient in TGF-β1 by Uncontrolled Flu-Like Syndrome¹

Sylvain Perruche^*,2,3, Pin Zhang^*,2, Takashi Maruyama^*, Jeffrey A. Bluestone, Philippe Saas and WanJun Chen^*,4

*Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892; University of California-San Francisco Diabetes Center, San Francisco, CA 94143; and INSERM UMR645, University of Franche-Comte, Establissement Francais du Sana de Bourgogne Franche Comte, Institut Federatif de Recherche 133, Besançon, France

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- 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.

⁴ Address correspondence and reprint requests to Dr. W. J. Chen, National Institute of Dental and Craniofacial Research/National Institutes of Health, 30 Convent Drive, Building 30, Room 304, Bethesda, MD 20892. E-mail address: wchen{at}mail.nih.gov

¹ This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research. P.S. is supported by grants from the Institut National du Cancer (PL098) and the Association de Recherche contre le Cancer (3851).

² S.P. and P.Z. contributed equally to this work.

³ Current address: INSERM UMR645, 1 Boulevard A Fleming, F-25020 Besançon, France.