NK Cells Contribute to the Control of<i>Trypanosoma cruzi</i>Infection by Killing Free Parasites by Perforin-Independent Mechanisms

Lieke, Thorsten; Graefe, Sebastian E. B.; Klauenberg, Ulricke; Fleischer, Bernhard; Jacobs, Thomas

doi:10.1128/iai.72.12.6817-6825.2004

Cited by 61 publications

(62 citation statements)

References 34 publications

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“…This result should be interpreted with caution, however, because it would be impossible to attribute the high susceptibility of the IL-12/IL-23 (p40) KO mice only to a defect of specific CD8 ϩ T cells. The absence of this cytokine impairs a number of other immunological functions, including the expansion of Th1 CD4 ϩ T cells and NKT and NK cells, all of which actively participate during the immune response to T. cruzi infection (7,15,23,30,42).…”

Section: Discussionmentioning

confidence: 99%

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 ⁺ T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

et al. 2011

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Recently, we described a heterologous prime-boost strategy using plasmid DNA followed by replicationdefective human recombinant adenovirus type 5 as a powerful strategy to elicit long-lived CD8 ؉ T-cellmediated protective immunity against experimental systemic infection of mice with a human intracellular protozoan parasite, Trypanosoma cruzi. In the present study, we further characterized the protective long-lived Genetic vaccination using the strategy known as the heterologous prime-boost regimen is being pursued as an alternative type of vaccine. This strategy consists of the use of two different vectors, both carrying a gene that encodes the same antigenic protein, for priming and boosting immunizations. This strategy can be particularly important in the case of intracellular pathogens and neoplastic cells, where the effectiveness of the vaccine relies heavily on its capacity to elicit specific immune responses mediated by cytotoxic CD8 ϩ T cells (reviewed in references 22, 31, 38, 39, and 57).

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Section: Discussionmentioning

confidence: 99%

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 ⁺ T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

et al. 2011

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“…Experimental models have shown that NK cells play a crucial role in immunity against T. cruzi (27). However, the role of NK cells during human T. cruzi infection is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Human Congenital Infection With Trypanosoma cruzi Induces Phenotypic and Functional Modifications of Cord Blood NK Cells

et al. 2006

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ABSTRACT:We studied the phenotype and activity of cord blood natural killer (NK) cells in newborns congenitally infected with Trypanosoma cruzi. We found that the proportion of CD56 bright NK cells was significantly decreased in cord blood from these newborns, suggesting they may have been recruited to secondary lymphoid organs. The remaining CD56bright NK cells exhibited a defective ability in the production of interferon (IFN)-␥ following in vitro activation with interleukin (IL)-12 ϩ IL-2 or IL-12 ϩ IL-15 cytokines, as compared with NK cells from uninfected newborns. In addition, cord blood NK cells from congenitally infected newborns stimulated with cytokines have a decreased release of granzyme B (GrB) when incubated with K562 target cells. This defect in cytotoxic effector function is associated with a reduced surface expression of activating NK receptors (NKp30, NKp46, and NKG2D) on CD56 dim NK cells compared with uninfected newborns. These alterations of fetal NK cells from congenitally infected newborns may reflect a down-regulation of the NK cell response after an initial peak of activation and could also be the result of T. cruzi modulating the immune response. (Pediatr Res 60: 38-43, 2006)

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“…However, these cells are thought to act early, secreting IFN-␥ (11,52). A role for cytolysis mediated by perforin has been discarded during NK direct contact-mediated lysis of T. cruzi or T. cruzi-infected cells (35,36). The role of NK cells in our system remains to be studied.…”

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confidence: 99%

Perforin and Gamma Interferon Expression Are Required for CD4⁺and CD8⁺T-Cell-Dependent Protective Immunity against a Human Parasite,Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination

et al. 2009

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A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4 ؉ and CD8 ؉ T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4 ؉ and CD8 ؉ T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-␥) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8 ؉ T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-␥ or IFN-␥/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-␥ in the presence of highly cytotoxic T cells. Vaccinated IFN-␥-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-␥ in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.

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NK Cells Contribute to the Control ofTrypanosoma cruziInfection by Killing Free Parasites by Perforin-Independent Mechanisms

Cited by 61 publications

References 34 publications

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 ⁺ T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 ⁺ T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

Human Congenital Infection With Trypanosoma cruzi Induces Phenotypic and Functional Modifications of Cord Blood NK Cells

Perforin and Gamma Interferon Expression Are Required for CD4⁺and CD8⁺T-Cell-Dependent Protective Immunity against a Human Parasite,Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination

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NK Cells Contribute to the Control ofTrypanosoma cruziInfection by Killing Free Parasites by Perforin-Independent Mechanisms

Cited by 61 publications

References 34 publications

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 + T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 + T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

Human Congenital Infection With Trypanosoma cruzi Induces Phenotypic and Functional Modifications of Cord Blood NK Cells

Perforin and Gamma Interferon Expression Are Required for CD4+and CD8+T-Cell-Dependent Protective Immunity against a Human Parasite,Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination

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Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 ⁺ T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

Heterologous Plasmid DNA Prime-Recombinant Human Adenovirus 5 Boost Vaccination Generates a Stable Pool of Protective Long-Lived CD8 ⁺ T Effector Memory Cells Specific for a Human Parasite, Trypanosoma cruzi

Perforin and Gamma Interferon Expression Are Required for CD4⁺and CD8⁺T-Cell-Dependent Protective Immunity against a Human Parasite,Trypanosoma cruzi, Elicited by Heterologous Plasmid DNA Prime-Recombinant Adenovirus 5 Boost Vaccination