Polyfunctional T Cell Responses in Children in Early Stages of Chronic Trypanosoma cruzi Infection Contrast with Monofunctional Responses of Long-term Infected Adults

Albareda, María Cecilia; Rissio, Ana María De; Tomás, Gonzalo; Serjan, Alicia; Alvarez, M; Viotti, Rodolfo; Fichera, Laura E.; Esteva, M; Potente, Daniel Fernando; Armenti, Alejandro; Tarleton, Rick L.; Laucella, Susana A.

doi:10.1371/journal.pntd.0002575

Cited by 41 publications

(47 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PMBCs stimulated with T. cruzi ‐lysate from children without evidence of cardiac involvement reported that the pool of antigenic‐specific T cells was enriched with CD4+/CD154+ and CD4+/TNF‐α+ T cells 29. In an adult population, we obtained similar frequencies for CD4+/CD154+ (mean 2.04% for all chagasic patients) and CD4+/membrane TNF‐α+ T cells (mean 3.06% in symptomatic patients).…”

Section: Discussionsupporting

confidence: 61%

“…In an adult population, we obtained similar frequencies for CD4+/CD154+ (mean 2.04% for all chagasic patients) and CD4+/membrane TNF‐α+ T cells (mean 3.06% in symptomatic patients). Interestingly, the same study demonstrated that the fraction of antigen‐specific T cells measured by surface CD4+/CD154+ and intracellular CD4+/TNF‐α+ T cells was almost undetectable in chronic adult chagasic patients with mild cardiac disease 29. Differences between previous studies could be explained by the antigen used (amastigote or trypomastigotes), time of incubation and stimulation, and method of cytokine detection (intracellular vs. membrane).…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 91%

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

View full text Add to dashboard Cite

show abstract

“…However, in spite of the control of parasitemia that allows the host to survive the acute stage of infection, the elicited immune response proves unable to prevent parasite colonization and evolution to the chronic phase of the disease, thus indicating only a partial success. Moreover, a CD4 T cell exhaustion process is observed during the progression of the infection, which might lead to worsening of the associated disease (51,52). In line with these findings, parasite-shed vesicles containing several components, including TS, make naive mice more susceptible to infection due to increased production of IL-4 and IL-10 (53).…”

Section: Discussionmentioning

confidence: 85%

Trypanosoma cruzitrans-Sialidase Prevents Elicitation of Th1 Cell Response via Interleukin 10 and Downregulates Th1 Effector Cells

et al. 2015

View full text Add to dashboard Cite

The trans-sialidases (TSs) from Trypanosoma cruzi, the agent of Chagas disease, are virulence factors shed to the bloodstream that induce strong alterations in the immune system. Here, we report that both enzymatically active TS (aTS) and its lectinlike isoform (iTS) disturb CD4 T cell physiology, inducing downregulation of Th1 cell functionality and in vivo cell expansion. By using ovalbumin-specific DO11.10 cells as tracers of clones developing the Th1 phenotype, we found that the infection induced significant amounts of gamma interferon (IFN-␥) but low levels of interleukin 2 (IL-2) and increased IL-4 production in vivo, in agreement with a mixed T helper response. The production of cytokines associated with the

show abstract

“…Even more, polyfunctional CD8 + T cells can provide protective immunity in vaccination studies against experimental T. cruzi infection (80)(81)(82). In Chagas disease, children with short-term T. cruzi infections exhibit a higher frequency of polyfunctional T cells in comparison with adults with long-term infections (83). We observed that asymptomatic patients have a higher frequency of polyfunctional parasite-specific CD8 + T cells, which could lead to more effective parasite control, whereas the monofunctional cytotoxic parasitespecific CD8 + T cells predominant in symptomatic patients could result in tissue damage.…”

Section: Cd8mentioning

confidence: 99%

Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients

Lasso

Mateus

Pavía

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8+ T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients. The results showed that patients at an advanced severe disease stage had a higher frequency of terminally differentiated CD8+ T cells than patients at an early stage of the disease. A monofunctional CD8+ T cell response was observed in patients at an advanced stage, whereas the coexpression of markers that perform three and four functions in response to parasite Ags was observed in patients at a less severe disease stage. The frequency of CD8+ T cells producing granzyme B and perforin and those expressing inhibitory receptors was higher in symptomatic patients than in asymptomatic patients. Taken together, these findings suggest that during the course of Chagas disease, CD8+ T cells undergo a gradual loss of function characterized by impaired cytokine production, the presence of advanced differentiation, and increased inhibitory receptor coexpression.

show abstract

Polyfunctional T Cell Responses in Children in Early Stages of Chronic Trypanosoma cruzi Infection Contrast with Monofunctional Responses of Long-term Infected Adults

Cited by 41 publications

References 40 publications

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

Trypanosoma cruzitrans-Sialidase Prevents Elicitation of Th1 Cell Response via Interleukin 10 and Downregulates Th1 Effector Cells

Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients

Contact Info

Product

Resources

About