| First Author | Perruche S | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 2 | Pages | 953-61 |
| PubMed ID | 19561097 | Mgi Jnum | J:151662 |
| Mgi Id | MGI:4354702 | Doi | 10.4049/jimmunol.0804076 |
| Citation | Perruche S, et al. (2009) Lethal effect of CD3-specific antibody in mice deficient in TGF-beta1 by uncontrolled flu-like syndrome. J Immunol 183(2):953-61 |
| abstractText | 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-beta1(-/-) mice. The death of TGF-beta1(-/-) 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-beta1 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-beta1 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-beta1(-/-) mice. |
