Contribution of NK, NK T, γδ T, and αβ T Cells to the Gamma Interferon Response Required for Liver Protection against<i>Trypanosoma cruzi</i>

Sardinha, Luiz Roberto; Elias, Rosa Maria; Mosca, Tainá; Bastos, Karina R. B.; Marinho, Cláudio R. F.; Lima, Maria Regina D'Império; Álvarez, José María

doi:10.1128/iai.74.4.2031-2042.2006

Cited by 61 publications

(60 citation statements)

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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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“…In addition, T. cruzi also infects the reticuloendothelial system including the liver, spleen, and bone marrow. [18][19][20][21]. The existence of an immunosuppressive activity exerted by MDSCs during acute T. cruzi infection has been previously reported [22].…”

Section: Introductionmentioning

confidence: 89%

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

et al. 2013

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Myeloid-derived suppressor cells (MDSCs Keywords: Inflammation r MDSCs r Nitric oxide r ROS r Trypanosoma cruziAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMyeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population consisting of immature macrophages, granulocytes, and dendritic cells as well as myeloid progenitor cells. They are considered to be one of the major components of the immune suppressive network responsible for suppressing T-cell responses in pathological conditions [1,2] as well as in the regulation of the immune response in healthy individuals [3]. These Correspondence: Dr. Susana Gea e-mail: sgea@fcq.unc.edu.ar myeloid cells are commonly identified in mice by the co-expression of the surface markers CD11b and Gr1 (Ly6G/Ly6C) and have been divided into two subsets: granulocytic (G) MDSCs with a CD11b + LY6G + LY6C low phenotype and monocytic (M) MDSCs with CD11b + LY6G − LY6C high phenotype [3,4]. Despite their morphological similarities, G-MDSCs and neutrophils are functionally and phenotypically different. G-MDSCs, but not neutrophils, are immunosuppressive and express higher levels of arginase-1 and myeloperoxidase than neutrophils, and also have increased production of reactive oxygen species (ROS) [5,6]. Although * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2014. 44: 184-194 Immunomodulation 185 M-MDSCs and inflammatory monocytes share the same phenotype and morphology, these cells are functionally distinct since M-MDSCs are highly immunosuppressive and they express high levels of both iNOS and arginase-1. Furthermore, although iNOS expression is a hallmark of a tumoricidal/microbicidal phenotype in M1 macrophages, iNOS promotes suppressive activities in M-MDSCs. This shift in iNOS activity most likely reflects the crosstalk of iNOS with other enzymes such as NADPH oxidase to promote the production of peroxynitrites, which inhibits the proliferation and effector function of T cells [2]. MDSCs use several mechanisms in addition to the production of ROS and NO, such as triggering apoptosis of activated T cells by depleting of L-arginine, via arginase [7][8][9][10]. There is also evidence that MDSCs may suppress immune activation by inducing T regulatory cell expansion [11]. Other suppressive mechanisms that have recently been proposed include the production of TGF-β [12,13], depletion of cysteine [8], induction of COX2 and prostaglandin E2 [1,[14][15][16].Trypanosoma cruzi an obligate intracellular protozoan, is the causative agent of Chagas disease. This disease affects about 20 million people in Latin America, with 120 million persons at risk. In the past decades, mainly as a result of increased migrations, the diagnosed cases have also increased in nonendemic countries such as Canada, United States of America, and Europe. This has led to an increased risk of transmission of the infection, mainly through blood transfusion and organ transplantation [17]. Pa...

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“…These data demonstrate that although mice lacking CD4 ϩ T cells developed decreased frequencies of TSKB20-specific CD8 ϩ T cells, the overall CD8 T-cell-depen- ϩ T cells expand in response to infection of CD4 ϩ T-cell-deficient mice, although generally not to the same extent as in wild-type mice (10,12,15,16,18,(24)(25)(26)34). It is possible that NK or ␥/␦ T cells, both of which are activated by T. cruzi infection, partially compensate for the absence of CD4 ϩ T-cell help (17,22). However, a lack of CD4 ϩ T-cell help during priming typically results in defective recall responses, poor protective capacity, and a loss of Ag-specific CD8 ϩ T cells over time (3,6,10,24,26).…”

Section: T-cell Help Provides In Vivo Evidence That T Cruzi Infectiomentioning

confidence: 99%

Limited Role for CD4 ⁺ T-Cell Help in the Initial Priming of Trypanosoma cruzi- Specific CD8 ⁺ T Cells

Padilla

Martin

et al. 2007

Infect Immun

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Immune control of the protozoan parasite Trypanosoma cruzi requires the activation of both CD4؉ and CD8 ؉ T cells. We recently identified two T. cruzi trans-sialidase peptides that are targets of approximately 30% of all CD8 ؉ T cells during acute T. cruzi infection in mice. To determine whether CD4 ؉ T cells are required for generation of these dominant CD8 ؉ T-cell responses, major histocompatibility complex class II (MHC II)-deficient mice were infected with the Brazil strain of T. cruzi and examined for the generation of antigenspecific CD8 ؉ T cells. Strong trans-sialidase TSKB18-and TSKB20-specific CD8 ؉ T-cell responses were generated in both the presence and the absence of CD4 ؉ help. However, the magnitudes of the immunodominant TSKB20-specific CD8 ؉ T-cell responses detectable using class I MHC-peptide tetramers were consistently lower in the blood and spleens of MHC II-deficient mice. Spleen cells from infected MHC II-deficient mice produced gamma interferon after in vitro stimulation with T. cruzi peptides at levels similar to those in wild-type mice, and MHC II-deficient mice displayed strong T. cruzi peptide-specific cytotoxic T-lymphocyte activity in vivo. Thus, primary CD8؉ T-cell responses in experimental T. cruzi infection are generated in the absence of CD4 ؉ T cells, providing further evidence that T. cruzi directly activates and licenses antigenpresenting cells. Nevertheless, unhelped CD8 ؉ T cells in T. cruzi-infected mice fail to reach the frequencies achieved in the presence of CD4 T-cell help and are unable to prevent acute-phase death of these mice.Trypanosoma cruzi is a kinetoplastid protozoan parasite that causes Chagas' disease in humans, one of the most important public health threats in Latin American countries (33). Both CD8 ϩ and CD4 ϩ T cells have been shown to be essential for the control of T. cruzi infection in experimental models; mice lacking either T-cell compartment, due to gene deletion of major histocompatibility complex (MHC) molecules and components (28, 29) or T-cell coreceptors (21) or to depletion of T cells using anti-CD4 or anti-CD8 antibodies (29), succumb to acute infection and display high systemic and tissue parasite loads (27). However, the role that CD4 ϩ T cells play in the development and regulation of CD8 ϩ T-cell immunity to T. cruzi remains to be determined.The requirement for CD4 ϩ T-cell help in the induction of CD8 ϩ T-cell responses has been studied in a number of murine models of infection, using MHC II knockout (KO) mice or mice depleted of CD4 ϩ T cells by injection of anti-CD4 antibody. CD4 ϩ T-cell activity is required for priming of the CD8 ϩ T-cell response to peptide-pulsed dendritic cells (DCs) (31) and for the optimal activation of pathogen-specific CD8 ϩ Tcell responses to Listeria monocytogenes (15) and influenza virus (19) infections. Nevertheless, strong primary CD8 ϩ T-cell responses against many infectious agents, such as lymphocytic choriomeningitis virus (12) or vesicular stomatitis virus (15), can be measured readily in animals l...

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Contribution of NK, NK T, γδ T, and αβ T Cells to the Gamma Interferon Response Required for Liver Protection againstTrypanosoma cruzi

Cited by 61 publications

References 62 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

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

Limited Role for CD4 ⁺ T-Cell Help in the Initial Priming of Trypanosoma cruzi- Specific CD8 ⁺ T Cells

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Contribution of NK, NK T, γδ T, and αβ T Cells to the Gamma Interferon Response Required for Liver Protection againstTrypanosoma cruzi

Cited by 61 publications

References 62 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

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

Limited Role for CD4 + T-Cell Help in the Initial Priming of Trypanosoma cruzi- Specific CD8 + T Cells

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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

Limited Role for CD4 ⁺ T-Cell Help in the Initial Priming of Trypanosoma cruzi- Specific CD8 ⁺ T Cells