Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypanosoma cruzi, the causative agent of Chagas' disease, suppresses immune responses during the acute phase and has been shown to induce multiple cellular alterations in activated human T lymphocytes. However, no information is available regarding the effects of this parasite on human B cells. Using an in vitro culture system, in which purified T. cruzi are co-cultured with either peripheral blood mononuclear cells (PBMC) or B-cell-enriched preparations (BCE), we studied whether the organism can induce alterations in DNA synthesis after stimulation with Pansorbin (PS). This response was markedly reduced by the parasite at both suboptimal and optimal PS concentrations, and the extent of the inhibition was augmented as the parasite concentration was increased. Maximal reduction in DNA synthesis was observed when the trypanosomes were incorporated into the cultures at 0 time (i.e. together with PS); the effect was of a much lesser magnitude and undetectable when the parasites were added at 24 and 48 hr, respectively. These results imply that T. cruzi affects a relatively early event during B-cell stimulation. This inference was confirmed by the finding that the proportion of PS-stimulated B cells expressing interleukin-2 (IL-2) receptors was significantly reduced when the parasite was present in the culture. Addition of recombinant human IL-2 did not restore B-cell responsiveness to normal levels. Suppressed B-cell responses were also observed when T. cruzi was separated from the PBMC or the BCE by a cell-impermeable filter, indicating that a soluble factor(s) released by the organism mediated the effect. Accordingly, supernatants of T. cruzi suspensions were found to be suppressive. These results demonstrate for the first time that T. cruzi can affect human B-cell responses and that the mechanism involves inhibition of IL-2 receptor expression.
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PMID:Trypanosoma cruzi induces suppression of DNA synthesis and inhibits expression of interleukin-2 receptors by stimulated human B lymphocytes. 174 80

Trypanosoma cruzi infection in humans and experimental animals often results in a chronic heart and gut inflammation and a dysfunction known as Chagas' disease. Previous studies have shown that the cellular infiltrate in the hearts of animals with chronic Chagas' disease consists mainly of CD8+ T cells. In this study, we have used immunohistochemical techniques to further characterize the immunological nature of chagasic heart lesions in three murine models of experimental Chagas' disease. Double-staining immunohistochemistry revealed that 10-30% of the infiltrating CD8+ T cells in the hearts of infected mice expressed the activation molecules, IL-2 receptor and CD44. In addition, large numbers of cells producing TNF-alpha, TGF-beta, IL-1 alpha, and IL-6 were consistently observed in the heart lesions, appearing during the acute infection and persisting throughout the chronic stage of infection (> 300 days). In contrast, IFN-gamma- and IL-10-producing cells were detected in relatively low numbers and only transiently between approximately 3 and 9 weeks postinfection. Cells producing IL-2, IL-4, and IL-5 were not observed in the hearts of mice at any point during the infection. The appearance of cytokine-producing cells in the hearts correlated with an increased local expression of class I and class II MHC molecules and adhesion molecules (ICAM-1, LFA-1, VLA-4, and VCAM-1). The results of this study suggest that the chronic inflammation in chagasic hearts is highly active and associated with a stable immunological pattern extending from the early acute stage of the infection through the late chronic stage. The pattern of cytokine production in heart is distinct from that observed in lymphoid organs and is not suggestive of an association between particular classes of cytokines and disease development. Instead it appears that both inflammatory and anti-inflammatory cytokines determine the pattern of the cellular response and the severity of disease in T. cruzi infection.
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PMID:Persistent production of inflammatory and anti-inflammatory cytokines and associated MHC and adhesion molecule expression at the site of infection and disease in experimental Trypanosoma cruzi infections. 893 70

During Trypanosoma cruzi infection the trans-sialidase superfamily stimulates the development of a large population of CD4 T lymphocytes that produces IFNgamma. These CD4 T cells fail to proliferate when stimulated in vitro. Why they fail to proliferate remains unclear. Nitric oxide is a critical component of the host immune response against T. cruzi, and to determine if NO inhibits trans-sialidase superfamily-specific proliferative responses, mice were fed either N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of inducible nitric oxide synthase (iNOS), or N(G)-nitro-D-arginine methyl ester (D-NAME), an inactive analog of L-NAME. The L-NAME-fed mice had increased parasitemia and mortality compared to the D-NAME-fed mice. Following stimulation with a T. cruzi trans-sialidase superfamily protein, splenocytes from both groups of mice failed to proliferate but continued to make similar amounts of IFNgamma, suggesting that the development of the trans-sialidase superfamily-specific CD4 response was not affected by iNOS inhibition. In addition, IL-2 receptor (IL-2R) expression was increased on T cells isolated from L-NAME-fed mice. These data suggest that during T. cruzi infection NO causes downregulation of IL-2R expression, but does not cause inhibition of trans-sialidase superfamily-specific CD4 T cell proliferation. Rather, the trans-sialidase superfamily proliferation may be inhibited by epitope variation.
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PMID:Trypanosoma cruzi: the effect of nitric oxide synthesis inhibition on the CD4 T cell response to the trans-sialidase superfamily. 1067 44

In this study, we document the development of stable, antigen-independent CD8+ T cell memory after drug-induced cure of a chronic infection. By establishing a system for drug cure of chronic Trypanosoma cruzi infection, we present the first extensively documented case of total parasite clearance after drug treatment of this infection. Cure resulted in the emergence of a stable, parasite-specific CD8+ T cell population with the characteristics of central memory cells, based upon expression of CD62L, CCR7, CD127, CD122, Bcl-2 and a reduced immediate in vivo CTL function. CD8+ T cells from treated and cured mice also expanded more rapidly and provided greater protection following challenge than those from chronically infected mice. These results show that complete pathogen clearance results in stable, antigen-independent and protective T cell memory, despite the potentially exhausting effects of prior long-term exposure to antigen in this chronic infection.
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PMID:Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease. 1842 31

CD8(+) T cell responses to persistent infections caused by intracellular pathogens are dominated by resting T effectors and T effector memory cells, with little evidence suggesting that a T central memory (T(CM)) population is generated. Using a model of Trypanosoma cruzi infection, we demonstrate that in contrast to the T effector/T effector memory phenotype of the majority of T. cruzi-specific CD8(+) T cells, a population of cells displaying hallmark characteristics of T(CM) cells is also present during long-term persistent infection. This population expressed the T(CM) marker CD127 and a subset expressed one or more of three other T(CM) markers: CD62L, CCR7, and CD122. Additionally, the majority of CD127(high) cells were KLRG1(low), indicating that they have not been repetitively activated through TCR stimulation. These CD127(high) cells were better maintained than their CD127(low) counterparts following transfer into naive mice, consistent with their observed surface expression of CD127 and CD122, which confer the ability to self-renew in response to IL-7 and IL-15. CD127(high) cells were capable of IFN-gamma production upon peptide restimulation and expanded in response to challenge infection, indicating that these cells are functionally responsive upon Ag re-encounter. These results are in contrast to what is typically observed during many persistent infections and indicate that a stable population of parasite-specific CD8(+) T cells capable of Ag-independent survival is maintained in mice despite the presence of persistent Ag.
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PMID:Stable CD8+ T cell memory during persistent Trypanosoma cruzi infection. 1868 55

Intravenous challenge with Trypanosoma cruzi can be used to investigate the process and consequences of blood parasite clearance in experimental Chagas disease. One hour after intravenous challenge of chronically infected mice with 5x10(6) trypomastigotes, the liver constituted a major site of parasite accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were visualized at this time point scattered in the liver parenchyma. Moreover, at this time, many of liver-cleared parasites were viable, as estimated by the frequency of positive cultures, which considerably diminished after 48 h. Following clearance, the number of infiltrating cells in the hepatic tissue notably increased: initially (at 24 h) as diffuse infiltrates affecting the whole parenchyma, and at 48 h, in the form of large focal infiltrates in both the parenchyma and perivascular spaces. Phenotypic characterization of liver-infiltrating cells 24 h after challenge revealed an increase in Mac1(+), CD8(+) and CD4(+) cells, followed by natural killer (NK) cells. As evidence that liver-infiltrating CD4(+) and CD8(+) cells were activated, increased frequencies of CD69(+)CD8(+), CD69(+)CD4(+) and CD25(+)CD122(+)CD4(+) cells were observed at 24 and 48 h after challenge, and of CD25(-)CD122(+)CD4(+) cells at 48 h. The major role of CD4(+) cells in liver protection was suggested by data showing a very high frequency of interferon (IFN)-gamma-producing CD4(+) cells 24 h after challenge. In contrast, liver CD8(+) cells produced little IFN-gamma, even though they showed an enhanced potential for secreting this cytokine, as revealed by in vitro T cell receptor (TCR) stimulation. Confirming the effectiveness of the liver immune response in blood parasite control during the chronic phase of infection, no live parasites were detected in this organ 7 days after challenge.
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PMID:The liver plays a major role in clearance and destruction of blood trypomastigotes in Trypanosoma cruzi chronically infected mice. 2005 69