Vγ1 γδ T cells regulate type-1/type-2 immune responses and participate in the resistance to infection and development of heart inflammation in Trypanosoma cruzi-infected BALB/c mice (original) (raw)
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2006
Many different cell populations or lineages participate in the resistance to Trypanosoma cruzi infection. gammadelta T cells may also take part in a network of interactions that lead to control of T. cruzi infection with minimal tissue damage by controlling alphabeta T cell activation, as was previously suggested. However, the gammadelta T cell population is not homogeneous and its functions might vary, depending on T cell receptor usage or distinct stimulatory conditions. In this study, we show that the in vivo depletion of V gamma 1-bearing gammadelta T cells, prior to the infection of BALB/c mice with the Y strain of T. cruzi, induces an increased susceptibility to the infection with lower amounts of IFN-gamma being produced by conventional CD4+ or CD8+ T cells. In addition, the production of IL-4 by spleen T cells in V gamma 1-depleted mice was increased and the production of IL-10 remained unchanged. Since V gamma 1(+) gammadelta T cell depletion diminished the conversion of na...
Chagas disease patients 3 4 Running title: Modulation of co-stimulatory molecules and cytokines by T. cruzi 5 6 Abstract 1 2 Interactions between macrophages and lymphocytes through co-stimulatory molecules and 3 cytokines are essential for mounting an efficient immune response, and controlling its 4 pathogenic potential. Here we demonstrate the immunomodulatory capacity of T. cruzi, the 5 causative agent of Chagas disease, through its ability to induce differential expression of 6 co-stimulatory molecules and cytokines by monocytes and T-cells. Co-stimulatory 7 molecule and cytokine modulation were evaluated using cells from non-infected individuals 8 and patients with the asymptomatic indeterminate, or the severe cardiac clinical forms of 9
Microbes and …, 2008
Recent reports have established an important role of CD4þCD25þ T cells in the immune regulation of infectious diseases, autoimmune disorders and cancer. In the present work, we investigated whether these cells had a regulatory role during Trypanosoma cruzi infection, using the Colombian strain. Inactivation of CD4þCD25þ cells in vivo conferred mice slightly more resistant to infection with the Colombian strain of T. cruzi, as evidenced by lower parasitemia and mortality rates. The augmented resistance to infection with Colombian strain did correlate with increased activation of effector CD4 cells. It was antibody-independent, since no difference in levels of IgM, IgG, IgG1 and IgG2a b recognizing T. cruzi antigens was observed throughout the infection of CD25-inactivated and control mice. Regarding pathogenesis, inflammatory infiltrate and frequency of CD4 and CD8 T cells or macrophages in the cardiac tissue was similar in both groups. Together, our data indicate that CD4þCD25þ cells have a limited role on host resistance during early T. cruzi infection. Despite exhaustive investigation, we did not observe any role for these regulatory cells in the pathogenesis of experimental chronic Chagas' disease.
The involvement of CD4+ CD25+ T cells in the acute phase of Trypanosoma cruzi infection
Microbes and …, 2008
The infection with Trypanosoma cruzi leads to a vigorous and apparently uncontrolled inflammatory response in the heart. Although the parasites trigger specific immune response, the infection is not completely cleared out, a phenomenon that in other parasitic infections has been attributed to CD4+CD25+ T cells (Tregs). Then, we examined the role of natural Tregs and its signaling through CD25 and GITR in the resistance against infection with T. cruzi. Mice were treated with mAb against CD25 and GITR and the parasitemia, mortality and heart pathology analyzed. First, we demonstrated that CD4+CD25+GITR+Foxp3+ T cells migrate to the heart of infected mice. The treatment with anti-CD25 or anti-GITR resulted in increased mortality of these infected animals. Moreover, the treatment with anti-GITR enhanced the myocarditis, with increased migration of CD4+, CD8+, and CCR5+ leukocytes, TNF-alpha production, and tissue parasitism, although it did not change the systemic nitric oxide synthesis. These data showed a limited role for CD25 signaling in controlling the inflammatory response during this protozoan infection. Also, the data suggested that signaling through GITR is determinant to control of the heart inflammation, parasite replication, and host resistance against the infection.
Vβ6-bearing T cells are involved in resistance to Trypanosoma cruzi infection in XID mice
International …, 1996
BALB.xld mice, carrying an X-linked mutation leading to the absence of CD5 + B cells, are highly resistant to Trypanosoma cruzi Infection. These mice clear blood parasites in the acute phase of infection and do not develop the inflammatory Infiltration characteristically observed in the chronic phase of susceptible strains of mice. We have shown that the resistance of BALB.x/d Is dependent on the production of high levels of IFN-y. Natural (adoptive foster) or artificial (In vivo infection of blocking antibodies) treatments of BALB.x/d induced deletion of CD4 + and CD8 + cells bearing V p 6 TCR. The absence of Vp6 lymphocytes considerably reduced resistance to infection. Furthermore, in BALB.x/d lacking this minor fraction of the T cell repertoire, almost 50% of the IFN-y production is lost. This indicates that Vp6-bearing T cells are either directly or Indirectly involved in the production of IFN-Y and > thus, important for an effective immune response during the acute phase of experimental Chagas' disease.
Brain, Behavior, and Immunity, 2014
We previously showed that Trypanosoma cruzi infection in C57BL/6 mice results in a lethal infection linked to unbalanced pro-and anti-inflammatory mediators production. Here, we examined the dynamics of CD4 + Foxp3 + regulatory T (Treg) cells within this inflammatory and highly Th1-polarized environment. Treg cells showed a reduced proliferation rate and their frequency is progressively reduced along infection compared to effector T (Teff) cells. Also, a higher fraction of Treg cells showed a naïve phenotype, meanwhile Teff cells were mostly of the effector memory type. T. cruzi infection was associated with the production of pro-and anti-inflammatory cytokines, notably IL-27p28, and with the induction of T-bet and IFN-c expression in Treg cells. Furthermore, endogenous glucocorticoids released in response to T. cruzi-driven immune activation were crucial to sustain the Treg/Teff cell balance. Notably, IL-2 plus dexamethasone combined treatment before infection was associated with increased Treg cell proliferation and expression of GATA-3, IL-4 and IL-10, and increased mice survival time. Overall, our results indicate that therapies aimed at specifically boosting Treg cells, which during T. cruzi infection are overwhelmed by the effector immune response, represent new opportunities for the treatment of Chagas disease, which is actually only based on parasite-targeted chemotherapy.
NK1.1 cells are required to control T cell hyperactivity during Trypanosoma cruzi infection
PubMed, 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 C57Bl/6 mice compared with untreated C57Bl/6 controls. Serum levels of IFN-gamma in anti-NK1.1-treated mice were higher than in non-depleted animals. Con-A-stimulated spleen cell supernatants from NK1.1 cell-depleted animals contained increased levels of IL-2 and nitric oxide (NO) during early infection. Conclusions: After the first week of infection, NO overproduction and high levels of IFN-gamma in anti-NK1.1-tre-ated C57Bl/6 mice appeared to be related to susceptibility and hyperactivation of peripheral T cells. Finally, this study suggests a novel regulatory function of NK1.1+ cells during T. cruzi infection. Without NK1.1 cells, T lymphocytes are hyperactivated but do not differentiate to effector/memory T cells in infected C57Bl/6 mice.
International Immunology, 1996
The role of T cell populations in immune control of Trypanosoma cruzi infection and subsequent development of disease has been examined using gene knockout mice deficient in the expression of either or both class I and class II MHC. Mice deficient in either class I-or class ll-restricted T cell populations show a striking similarity in their mortality rate, parasite load and tissue inflammatory response following infection with the Brazil strain of T. cruzi. In both cases, all animals died during the acute phase of the infection with high parasitemias and high parasite loads in the heart and skeletal muscle, but with reduced tissue inflammatory responses. Mice deficient in both class I and class II MHC expression demonstrated even higher numbers of circulating and tissue parasites, essentially non-existent tissue inflammatory responses, and succumbed to infection earlier than single-deficient mice. MHC class l-deficient mice which survive into the chronic phase following infection with the M/78 or M/80 clones of T. cruzi have both relatively higher tissue parasite loads and more extensive and severe inflammatory responses than control immunocompetent mice. Immunologically, the acute infection in the double-deficient mice was accompanied by a marked increase in CD4~CD8~ a|3TCR + cells in the spleen. Surprisingly, both class I-and class ll-deficient mice produced detectable but sub-normal levels of anti-parasite antibodies while double-deficient mice produced little to no detectable anti-parasite antibody. These results establish the importance of both class I-and class ll-restricted T cells in immune control of circulating blood stages and intracellular states of T. cruzi. In addition, this work reinforces the relationship between tissue parasite load and the severity of the inflammatory lesions in chronically infected animals.