Differential susceptibilities of mice genomically deleted of CD4 and CD8 to infections with Trypanosoma cruzi or Trypanosoma brucei

Rottenberg, Martı́n E.; Bakhiet, Moiz; Olsson, Tomas; Kristensson, Krister; Mak, Tak W.; Wigzell, Hans; Örn, Anders

doi:10.1128/iai.61.12.5129-5133.1993

Cited by 132 publications

(62 citation statements)

References 28 publications

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“…This priming occurred early after parasite inoculation-at the moment of exponential increase of the parasitaemia-and persisted during the chronic phase of the disease. By in vivo depletion of cells were shown to be involved in resistance against the parasite [30,31]. In the present model, the very high levels of IFN-induced by the injection of anti-CD3 MoAb are detrimental, as they are involved in the development of a severe shock syndrome.…”

Section: Discussionmentioning

confidence: 68%

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Jacobs

Dubois

Carlier

et al. 1996

Clinical and Experimental Immunology

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SUMMARYThe 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-) and tumour necrosis factoralpha (TNF-). As these cytokines are known to be involved in the host defence against Trypanosoma cruzi, we measured serum levels of IFN-and TNF-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-and TNF-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-and TNF-. 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-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-or TNF-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-and TNF-.

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Section: Discussionmentioning

confidence: 68%

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Jacobs

Dubois

Carlier

et al. 1996

Clinical and Experimental Immunology

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“…In late coinfected animals there was no specific production of IFN-g which could explain the increase in susceptibility detected in this group, since IFN-g seems necessary to provide protection against T. cruzi (Cardillo et al 1996, Golden & Tarleton 1991, Tarleton 1991, Torrico et al 1991, Silva et al 1992, Hunter et al 1996. However, even a high endogenous production of this cytokine seems insufficient to protect against this parasite (Golden & Tarleton 1991, Volume 21, Number 4, April 1999 Previous infection alters susceptibility to T. cruzi Rottenberg et al 1993, Zhang & Tarleton 1996 when it is not accompanied by other cytokines such as IL-4 or even a complex mixture composed of at least IL-2, IL-3, IL-4 and IL-5 (Golden et al 1991). Accordingly, the only stage at which we found no or very low numbers of parasites compared to single infected mice was when IFN-g and IL-4 were both specifically produced at high levels in early coinfected animals (Figures 1, 4d,e, day 9), whereas a decrease in IL-4 secretion in this same group was related to an increase in the number of parasites (Figures 1 and 4e, day 27).…”

Section: Discussionmentioning

confidence: 88%

Susceptibility to Trypanosoma cruzi is modified by a previous non‐related infection

Rodríguez

Terrazas

Marquez

et al. 1999

Parasite Immunology

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Helminth infections are frequently massive, chronic and strong inductors of Th2-type cytokines. This implies that infection by such parasites could alter the susceptibility to subsequent infections by other pathogens, particularly intracellular parasites. We therefore explored whether a persistent infection, caused by Taenia crassiceps cysticerci, in BALB/c mice could affect susceptibility to a later infection by Trypanosoma cruzi. We found that the presence of the cysticerci indeed modified the immune response and the susceptibility to T. cruzi, and that these modifications depended on the time-course evolution of the initial infection. Coinfection with the protozoan in the early stages of the helminth infection, induced a delay on the onset of parasitaemia, early specific production of IFN-gamma and high specific production of IL-4. A significant increase in susceptibility to T. cruzi was observed only when mice were coinfected in late stages when the helminth load is greater and a Th2 type response against it is predominant. The in vitro specific response to T. cruzi antigens was then characterized by low levels of both IFN-gamma and IL-4. These findings suggest that chronic helminth infections could potentially have a significant influence over the immune response and hence susceptibility to other pathogens.

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“…Thus, during infections with the extracellular parasite T. brucei brucei, IFN-7 may promote parasitic growth in a host animal both directly by stimulating trypanosome proliferation and indirectly by its immunosuppresive effects. This contrasts the protective effects of IFN-7 observed during viral infections or during infections with the intracellular parasite T. cruzei [11]. Immunoglobulins obtained from rats 6 days p.i.…”

mentioning

confidence: 76%

Increased Levels of Antibodies to IFN‐γ in Human and Experimental African Trypanosomiasis

Bonfanti

Caruso

Bakhiet³

et al. 1995

Scand J Immunol

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In African trypanosomiasis the occurrence of antibodies to interferon-gamma (IFN-gamma) was studied in both humans and experimental rats. Sera from patients infected with Trypanosoma brucei gambiense showed increased levels of antibodies to IFN-gamma as compared with controls from the same regions in Africa. In Sprague-Dawley rats infected with Trypanosoma brucei brucei an early appearance of IFN-gamma-producing spleen cells was observed, followed by an increase in levels of antibodies against IFN-gamma in the sera. Previously, IFN-gamma has been found to play a crucial role in trypanosome infections in rats by promoting proliferation of Trypanosoma brucei brucei. The appearance of antibodies to IFN-gamma in humans, as in rats, indicates that this cytokine is produced also in the human infection. Its parasitic growth-stimulating and pathophysiological effects on the organism may be reduced by the antibodies.

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Differential susceptibilities of mice genomically deleted of CD4 and CD8 to infections with Trypanosoma cruzi or Trypanosoma brucei

Cited by 132 publications

References 28 publications

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Susceptibility to Trypanosoma cruzi is modified by a previous non‐related infection

Increased Levels of Antibodies to IFN‐γ in Human and Experimental African Trypanosomiasis

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