Document 0217
 DOCN  M9650217
 TI    Administration of anti-CD3 monoclonal antibody during experimental
       Chagas' disease induces CD8+ cell-dependent lethal shock.
 DT    9605
 AU    Jacobs F; Dubois C; Carlier Y; Goldman M; Laboratoire Pluridisciplinaire
       de Recherche Experimentale; Biomedicale, Hopital Erasme, Brussels,
       Belgium.
 SO    Clin Exp Immunol. 1996 Feb;103(2):233-8. Unique Identifier : AIDSLINE
       MED/96152670
 AB    The injection of the 145-2C11 anti-CD3 MoAb in mice induces a polyclonal
       T cell activation resulting in the release of several cytokines,
       including interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha
       (TNF-alpha). As these cytokines are known to be involved in the host
       defence against Trypanosoma cruzi, we measured serum levels of IFN-gamma
       and TNF-alpha after injection of the 145-2C11 MoAb in the course of
       experimental murine Chagas' disease. Compared with control mice, T.
       cruzi-infected BALB/c mice were found to be primed to secrete very high
       levels of IFN-gamma and TNF-alpha from the second and the first week of
       infection, respectively, up to the chronic phase. In vivo cell depletion
       experiments indicated that CD8+ T cells were responsible for these
       dramatic hyperproductions of IFN-gamma and TNF-alpha. While all control
       mice survived anti-CD3 MoAb injection, a high lethality rate was
       observed in T. cruzi-infected mice within 24 h after anti-CD3 MoAb
       challenge. Pretreatment with neutralizing anti-IFN-gamma MoAb or
       depletion of CD8+ T cell population dramatically decreased the mortality
       induced by anti-CD3 MoAb in T. cruzi-infected mice. Finally, we showed
       that anti-CD3 MoAb injection in T. cruzi-infected mice was followed by a
       massive release of nitric oxide (NO) metabolites, which was partially
       reduced by IFN-gamma or TNF-alpha neutralization. The administration of
       the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME)
       before anti-CD3 MoAb challenge did not prevent and even enhanced
       lethality in T. cruzi-infected mice, suggesting that NO overproduction
       and lethal shock are not causally related. We conclude that injection of
       anti-CD3 MoAb in the course of experimental Chagas' disease induces a
       CD8+ cell-dependent shock mediated by IFN-gamma and TNF-alpha.
 DE    Animal  Antibodies, Monoclonal/*ADMINISTRATION & DOSAGE  Antigens,
       CD3/*IMMUNOLOGY  Antigens, CD8/*IMMUNOLOGY  Chagas
       Disease/*IMMUNOLOGY/PHYSIOPATHOLOGY  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/IMMUNOLOGY  Disease
       Models, Animal  Female  Interferon Type II/BIOSYNTHESIS  Mice  Mice,
       Inbred BALB C  Shock/*IMMUNOLOGY  Support, Non-U.S. Gov't  Tumor
       Necrosis Factor/BIOSYNTHESIS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).