NK1.1+ Cells and T-Cell Activation in Euthymic and Thymectomized C57Bl/6 Mice during Acute Trypanosoma cruzi Infection (original) (raw)
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NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection
Medical science monitor : international medical journal of experimental and clinical research, 2004
BACKGROUND This study evaluated the regulatory function of NK1.1+ cells during Trypanosoma cruzi infection. MATERIAL/METHODS Both thymectomized (Tx C57Bl/6) and euthymic C57Bl/6 mice (C57Bl/6) were infected intraperitoneally with the Tulahuen strain. NK1.1+ cells were depleted in vivo by anti-NK1.1 mAb. Spleen cells were analyzed by flow cytometry for the expression of CD44 and CD69 on T cells. Supernatants from splenocytes were used to measure nitrite concentration (quantified by Griess reagent). Interleukin 2 and IFN-gamma levels were determined by ELISA. The protocols used herein were approved by the Institutional Committee for Ethics. Student's t or Kruskal-Wallis tests were applied, as indicated. RESULTS The number of T cells expressing CD69 increased progressively during T. cruzi infection in NK1.1 cell-depleted C57Bl/6 mice. In spite of an increased early T cell activation during infection, the percentage of CD4+ CD44high T cells did not augment in NK1.1 cell-depleted C57...
Scandinavian Journal of Immunology, 1988
T lymphocytes provide a mitjor line of defence iigainsi many protozoiin parasites. The aim of this work was lo determine the role of T-cell helper/inducersuhsei (T h/i) in the resistance to Trypanosoma cruzi in a murine model. The importance of natural killer (NK) cells in the resistance lo lhe parasite was also evaluated. BALB/c and C57BL/6 mice were injected with either monoclonal antibodies against LJT4. Thy 1.2. NKl.l. ur with a polycional rabbit antiscrum against NK cells (anti-asialo GM-1). The effect of in vivo administration of these antibodies was tested in separate functional assays. After antibody treatment, mice were infected with a low dose of T. cruzi m Ihe bloodsircam form. Mice depleted of. or reduced inT, T h/i. or NK cell activity all developed higher parasitaemia and had higher mortality than their control counterparts. Mice injected wilh anti-L3T4 monoclonal antibodies were unable to generate a specific antibody response to the parasite. Treatment of mice with alpha/beta interferon, which is known to boost NK cell activiiy, resulted in an enhiinced resislancc to Ihe para.site. Our data indicate that V h/i cells as well as NK eells are of viial importance in conirolling parasitaemia and reducing mortality in T. cnizf-infected mice. Finally, we also demonstrate that the production of antibodies specific for T. cruzi is strictly T helper ceildependent.
1996
Gamma interferon (IFN-␥) plays an important role in experimental Trypanosoma cruzi infections, presumably by controlling the early replication of parasites in host macrophages. In this work, we show that NK cells represent an important cell type responsible for the production of most of the IFN-␥ in the early stages of T. cruzi infection and that the in vivo treatment of mice with anti-NK1.1 monoclonal antibody made resistant animals susceptible to the infection. Through in vitro experiments, we demonstrate that normal splenocytes from euthymic or athymic nude mice cultivated for 48 h with live T. cruzi trypomastigotes produced elevated levels of IFN-␥. In addition, NK-depleted splenocytes show a drastic reduction of IFN-␥ production in response to live T. cruzi trypomastigotes. We also demonstrate that IFN-␥ production is dependent on a factor secreted by adherent cells. Supernatants of spleen cells from athymic nude mice are able to induce IFN-␥ production by normal splenocytes when cultured with trypomastigotes. The addition of anti-interleukin-10 to these cultures resulted in a marked increase in IFN-␥ production. On the other hand, the absence of NK cells led to an increased secretion of interleukin-10 upon in vitro stimulation with T. cruzi. Taken together, these results suggest that NK cells are the major source of IFN-␥ that could be involved in limiting the replication of T. cruzi in host macrophages during the early acute phase of the infection.
Regulation of Trypanosoma cruzi infection and interleukin 10: role of NK cells
Infection and Immunity
Gamma interferon (IFN-␥) plays an important role in experimental Trypanosoma cruzi infections, presumably by controlling the early replication of parasites in host macrophages. In this work, we show that NK cells represent an important cell type responsible for the production of most of the IFN-␥ in the early stages of T. cruzi infection and that the in vivo treatment of mice with anti-NK1.1 monoclonal antibody made resistant animals susceptible to the infection. Through in vitro experiments, we demonstrate that normal splenocytes from euthymic or athymic nude mice cultivated for 48 h with live T. cruzi trypomastigotes produced elevated levels of IFN-␥. In addition, NK-depleted splenocytes show a drastic reduction of IFN-␥ production in response to live T. cruzi trypomastigotes. We also demonstrate that IFN-␥ production is dependent on a factor secreted by adherent cells. Supernatants of spleen cells from athymic nude mice are able to induce IFN-␥ production by normal splenocytes when cultured with trypomastigotes. The addition of anti-interleukin-10 to these cultures resulted in a marked increase in IFN-␥ production. On the other hand, the absence of NK cells led to an increased secretion of interleukin-10 upon in vitro stimulation with T. cruzi. Taken together, these results suggest that NK cells are the major source of IFN-␥ that could be involved in limiting the replication of T. cruzi in host macrophages during the early acute phase of the infection.
Clinical and experimental immunology, 2000
Early immunological activation involves an initial phase of cytokine activity and involvement of cell types such as NK cells. Such early immune responses are often decisive in resolution of microbial infection. NK cells reduce parasitaemia and enhance survival in experimental Trypanosoma cruzi infection, although the nature of these protective effects is not well understood. In this study, a detailed analysis of innate cytokine induction in the absence and presence of NK cells during the first 8 days of infection was performed. Following intraperitoneal infection with a high dose of parasites, reverse transcriptase-polymerase chain reaction showed that splenic mRNA for IFN-g appeared as a peak 24 h after infection and then reappeared 2±3 days later. In NK-depleted animals the first peak of IFN-g was absent and the second wave was slightly delayed. mRNA for IL-12 and tumour necrosis factor-alpha (TNF-a ) as well as IFN-a protein in serum was only recorded 24 h after infection, at the same time as the IFN-g peak. NK depletion resulted in a small decrease of IL-12 mRNA levels, whereas TNF-a and IFN-a were not affected. NK cytotoxicity remained elevated throughout the 8 days and thus did not parallel the expression of IFN-g production by NK cells. We conclude that NK cell cytokine production and cytolytic activity play different roles in response to challenge with T. cruzi.
Clinical and Experimental Immunology, 2000
SUMMARYEarly immunological activation involves an initial phase of cytokine activity and involvement of cell types such as NK cells. Such early immune responses are often decisive in resolution of microbial infection. NK cells reduce parasitaemia and enhance survival in experimental Trypanosoma cruzi infection, although the nature of these protective effects is not well understood. In this study, a detailed analysis of innate cytokine induction in the absence and presence of NK cells during the first 8 days of infection was performed. Following intraperitoneal infection with a high dose of parasites, reverse transcriptase-polymerase chain reaction showed that splenic mRNA for IFN-γ appeared as a peak 24 h after infection and then reappeared 2–3 days later. In NK-depleted animals the first peak of IFN-γ was absent and the second wave was slightly delayed. mRNA for IL-12 and tumour necrosis factor-alpha (TNF-α) as well as IFN-α protein in serum was only recorded 24 h after infection, ...
International immunology, 1998
We have previously shown that splenic gammadelta T cells from young but not aged BALB/c mice possess suppressor activity in vivo and in vitro during the acute phase of Trypanosoma cruzi infection. The present work was undertaken to investigate the suppressor activity of gammadelta T cells from T. cruzi-infected euthymic or athymic mice and the role of the thymus in modulating non-adherent spleen cell suppressor activity during the acute phase of infection. Splenic gammadelta T cells from aged or athymic BALB/c mice reconstituted with total spleen cells or non-reconstituted did not exhibit suppressor activity when added to full allogeneic, mixed lymphocyte cultures. In contrast, splenic gammadelta T cells from young euthymic BALB/c mice showed suppressor activity in vitro. Thymectomy reduced the splenic gammadelta T cell suppressor activity of young BALB/c mice in a time-dependent manner, following a T. cruzi challenge. The continuous provision of thymocytes to aged mice, young thyme...
Parasite Immunology, 2013
SummaryEarly interferon‐gamma (IFN‐γ) release by innate cells is critical to direct type 1 immune response able to control intracellular pathogens like Trypanosoma cruzi. Although CD56bright natural killer (NK) cells are reported to be potent early IFN‐γ producers, other CD56+ cells like CD56dim NK cells and NK‐like T cells have recently been shown to also release IFN‐γ. We have here studied the contribution of each CD56+ lymphocyte populations in early IFN‐γ production in both adults and neonates. On this purpose, we analysed the kinetics of IFN‐γ production by RT‐PCR, ELISA and flow cytometry from 2 h onwards after T. cruzi and IL‐15 stimulation and sought for the responding CD56+ cells. CD56bright and CD56dimCD16− NK cells were the more potent IFN‐γ early producers in response to IL‐15 and parasites in adults and neonates. In both age groups, the majority of IFN‐γ producing cells were NK cells. However, on the contrary to neonates, CD3+CD56+ NK‐like T cells and CD3+CD56− ‘classic...
Infection and Immunity - INFEC IMMUNITY, 2006
In the present work, we show that intracellular Trypanosoma cruzi is rarely found in the livers of acutely infected mice, but inflammation is commonly observed. The presence of numerous intrahepatic amastigotes in infected gamma interferon (IFN-)-deficient mice corroborates the notion that the liver is protected by an efficient local immunity. The contribution of different cell populations was suggested by data showing that CD4- and CD8-deficient mice were able to restrain liver parasite growth. Therefore, we have characterized the liver-infiltrating lymphocytes and determined the sources of IFN- during acute T. cruzi infection. We observed that natural killer (NK) cells increased by day 7, while T and B cells increased by day 14. Among CD3 cells, CD4, CD8, and CD4 CD8 cell populations were greatly expanded. A large fraction of CD3 cells were positive for PanNK, a 1 integrin expressed by NK and NK T cells. However, these lymphocytes were not classic NK T cells because they did not e...