Natural CD4<sup>+</sup> T‐cell responses against <i>Trypanosoma cruzi</i> KMP‐11 protein in chronic chagasic patients

Cuéllar, Adriana; Rojas, Francia; Bolaños, Natalia I.; Díez, Hugo; Thomas, María Carmen; Rosas, Fernando; Velasco, V R; López, Manuel Carlos López; González, John Mario; Puerta, Concepción J.

doi:10.1038/icb.2008.92

Cited by 3 publications

(5 citation statements)

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“…The acute phase of the infection is followed by a chronic phase with the presence of a low level parasitemia. CD4þ and CD8þ T lymphocytes participate in the control but not the elimination of T. cruzi, as consistently demonstrated in animal models and human infection [14][15][16]. Approximately 30% of chronically infected individuals become symptomatic due to heart or gastrointestinal involvement [17].…”

Section: Introductionmentioning

confidence: 83%

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

Ripoll

Giraldo

Bolaños

et al. 2017

Immunity Inflam & Disease

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IntroductionChagas disease is a parasitic infection whose pathogenesis is related to parasite persistence and a dysfunctional cellular immune response. Variability in cytokine secretion among chronic Trypanosoma cruzi‐infected patients might preclude the identification of the pool of antigen specific T cells. The goal of this study was to determine the fraction of T cells responding to T. cruzi antigen measured by the expression of membrane TNF‐α and CD154.MethodsA total of 21 chagasic patients, 11 healthy and 5 non‐chagasic cardiomyopathy controls were analyzed. PBMCs were short‐term cultured in the presence of anti‐CD28, anti‐CD49d, anti‐TNF‐α, and TACE (TNF‐α converting enzyme) inhibitor either under T. cruzi‐lysate or polyclonal stimuli. Cells were stained with anti‐CD3, anti‐CD4, anti‐CD8, and anti‐CD154, and analyzed with flow cytometry.ResultsCD4+ and CD8+ T cells in chagasic patients displayed higher percentages of membrane‐bound TNF‐α+ and CD154+ compared with controls after T. cruzi‐antigen stimulation. Both markers displayed a positive correlation in the T cell subpopulations analyzed. Symptomatic chagasic patients were differentiated from asymptomatic patients based on the expression of CD154 and membrane TNF‐α in TCD4+ and TCD8+ compartments, respectively.ConclusionsThese results show that both markers could be useful for assessing the pool of antigen‐specific T cells in chronic chagasic patients.

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Section: Introductionmentioning

confidence: 83%

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

Ripoll

Giraldo

Bolaños

et al. 2017

Immunity Inflam & Disease

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“…The description of new class II epitopes is a key contribution of this work, as the study of these cells' specificity in Chagas' disease is far less documented than that of CD8 + T cells. Until the production of this article, T. cruzi proteins known to activate a Th response in Chagas' disease patients were KMP-11 (17), Tc24, and TSA-1 (18). Abel and collaborators (19) had also determined that several variants of a peptide from repetitive Ag B13 are presented to CD4 + T cells in the context of HLA-DQA1*05:01-DQB1*03:01, and some of these variants trigger proliferation specifically in cells from T. cruzi-infected patients.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, cruzipain, kinetoplastid membrane protein 11 (KMP-11), heat shock protein 70 (HSP-70), putative surface Ag TcCA-2, and several members of the trans-sialidase superfamily of proteins have been reported as sources of epitopes recognized by human CD8 + T cells (11)(12)(13)(14)(15). The specificity of T. cruzi-specific CD4 + T cells has been studied to a far lesser extent (16), and only a few proteins (trypomastigote surface Ag 1 [TSA-1], Tc24, Ag B13, and KMP -11) have been demonstrated to induce a recall response on CD4 + T cells cells from chronic patients (17)(18)(19).…”

Section: The Journal Of Immunologymentioning

confidence: 99%

In Silico Guided Discovery of Novel Class I and II Trypanosoma cruzi Epitopes Recognized by T Cells from Chagas’ Disease Patients

Acevedo

Juiz

Ziblat

et al. 2020

The Journal of Immunology

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T cell–mediated immune response plays a crucial role in controlling Trypanosoma cruzi infection and parasite burden, but it is also involved in the clinical onset and progression of chronic Chagas’ disease. Therefore, the study of T cells is central to the understanding of the immune response against the parasite and its implications for the infected organism. The complexity of the parasite–host interactions hampers the identification and characterization of T cell–activating epitopes. We approached this issue by combining in silico and in vitro methods to interrogate patients’ T cells specificity. Fifty T. cruzi peptides predicted to bind a broad range of class I and II HLA molecules were selected for in vitro screening against PBMC samples from a cohort of chronic Chagas’ disease patients, using IFN-γ secretion as a readout. Seven of these peptides were shown to activate this type of T cell response, and four out of these contain class I and II epitopes that, to our knowledge, are first described in this study. The remaining three contain sequences that had been previously demonstrated to induce CD8+ T cell response in Chagas’ disease patients, or bind HLA-A*02:01, but are, in this study, demonstrated to engage CD4+ T cells. We also assessed the degree of differentiation of activated T cells and looked into the HLA variants that might restrict the recognition of these peptides in the context of human T. cruzi infection.

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“…Only a few proteins have been demonstrated to induce a recall response on CD4 + T cells from T. cruzi infected-individuals in the chronic phase of the disease ( 38 , 49 , 52 , 76 , 77 ).…”

Section: Cd4 + T Cell Specificity In Chagas Diseasementioning

confidence: 99%

“…Concerning KMP-11, a specific CD4 + T cell response was shown as INF-γ production upon the stimulation of PBMC from chronic Chagas disease patients with the recombinant antigen ( 76 ). KMP-11 responders were mostly patients with severe cardiomyopathy (abnormal ECG and cardiomegaly in chest radiography) whereas only one subject was determined as responder out of eight evaluated donors in patients with normal findings on ECG, or abnormal ECG and no cardiac enlargement ( 76 ).…”

Section: Cd4 + T Cell Specificity In Chagas Diseasementioning

confidence: 99%

T Cell Specificity: A Great Challenge in Chagas Disease

2021

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The CD4+ and CD8+ T cell immune response against T. cruzi, the parasite causing Chagas disease, are relevant for both parasite control and disease pathogenesis. Several studies have been focused on their phenotype and functionally, but only a few have drilled down to identify the parasite proteins that are processed and presented to these cells, especially to CD4+ T lymphocytes. Although approximately 10,000 proteins are encoded per haploid T. cruzi genome, fewer than 200 T cell epitopes from 49 T. cruzi proteins have been identified so far. In this context, a detailed knowledge of the specific targets of T cell memory response emerges as a prime tool for the conceptualization and development of prophylactic or therapeutic vaccines, an approach with great potential to prevent and treat this chronic disease. Here, we review the available information about this topic in a comprehensive manner and discuss the future challenges in the field.

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Natural CD4⁺ T‐cell responses against Trypanosoma cruzi KMP‐11 protein in chronic chagasic patients

Cited by 3 publications

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T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

In Silico Guided Discovery of Novel Class I and II Trypanosoma cruzi Epitopes Recognized by T Cells from Chagas’ Disease Patients

T Cell Specificity: A Great Challenge in Chagas Disease

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Natural CD4+ T‐cell responses against Trypanosoma cruzi KMP‐11 protein in chronic chagasic patients

Cited by 3 publications

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T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

T cells responding to Trypanosoma cruzi detected by membrane TNF‐α and CD154 in chagasic patients

In Silico Guided Discovery of Novel Class I and II Trypanosoma cruzi Epitopes Recognized by T Cells from Chagas’ Disease Patients

T Cell Specificity: A Great Challenge in Chagas Disease

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Natural CD4⁺ T‐cell responses against Trypanosoma cruzi KMP‐11 protein in chronic chagasic patients