Progressive Activation of CD127+132− Recent Thymic Emigrants into Terminally Differentiated CD127−132+ T-Cells in HIV-1 Infection

Sasson, Sarah C.; Zaunders, John; Seddiki, Nabila; Bailey, Michelle; McBride, Kristin; Koelsch, Kersten K.; Merlin, Kate; Smith, Don; Cooper, David A.; Kelleher, Anthony D.

doi:10.1371/journal.pone.0031148

Cited by 8 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been shown that CD127 - CD132 + T cells are mainly comprised by short-live effector T cells (25), concurring with the high frequencies of total effector CD4 and CD8 T cells found in chronically T. cruzi -infected subjects (3,4). Despite that patients in the chronic phase of the infection, including those with more severe forms of the disease, display an activated immune status (3,4, 26-29), herein we show that the capability to modulate IL7R receptor components are impaired in more severe clinical stages.…”

Section: Discussionsupporting

confidence: 58%

Perturbed T Cell IL-7 Receptor Signaling in Chronic Chagas Disease

Albareda

Pérez‐Mazliah

Natale

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections with signs of T cell exhaustion. Alterations in cytokine receptor signal transduction have emerged as one of the cell-intrinsic mechanisms of T cell exhaustion. Herein, we performed an analysis of the expression of IL-7R components (CD127 and CD132) on CD4+ and CD8+ T cells, and evaluated IL-7-dependent signaling events in patients at different clinical stages of chronic chagasic heart disease. Subjects with no signs of cardiac disease showed a decrease in CD127+CD132+ cells and a reciprocal gain of CD127-CD132+ in CD8+ and CD4+ T cells compared to either patients exhibiting heart enlargement or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of CD127 and the upregulation of CD132 on T cells. IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were lower in T. cruzi-infected subjects compared with uninfected controls. The serum levels of IL-7 was also increased in chronic chagasic patients. The present study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a potential mechanism of T cell exhaustion in chronic T. cruzi infection.

show abstract

Section: Discussionsupporting

confidence: 58%

Perturbed T Cell IL-7 Receptor Signaling in Chronic Chagas Disease

Albareda

Pérez‐Mazliah

Natale

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…CD45RA + T cells are primarily comprised of naïve and terminally differentiated effector T cells [27, 28]. We measured the proportion of recent thymic emigrant cells (RTE) (i.e., CD127 + CD132 — ) and terminally differentiated T cells (TTE) (i.e., CD127 — CD132 + ) [29–30] among CD45RA + T cells based on the expression of CD127 and CD132. IFN-γ producers in patients with cardiac disease (i.e., subjects in the G1, G2 and G3 clinical groups) exhibited lower frequencies of RTE in the CD4 + and CD8 + T-cell compartments compared with IFN-γ nonproducers and uninfected subjects (Fig 2A and 2B).…”

Section: Resultsmentioning

confidence: 99%

Trypanosoma cruzi-specific IFN-γ-producing cells in chronic Chagas disease associate with a functional IL-7/IL-7R axis

et al. 2018

View full text Add to dashboard Cite

BackgroundThe severity of cardiac disease in chronic Chagas disease patients is associated with different features of T-cell exhaustion. Here, we assessed whether the ability of T cells to secrete IFN-γ in response to T. cruzi was linked to disruption in immune homeostasis and inflammation in patients with chronic Chagas disease.Methodology/Principal findingsPBMCs from chronic Chagas disease patients and uninfected controls were examined for frequencies of T. cruzi-responsive IFN-γ-producing cells by ELISPOT and cellular expression and function of IL-7R using flow cytometry. Serum levels of IL-7, IL-21, IL-27, soluble IL-7R, and inflammatory cytokines were also evaluated by ELISA or CBA techniques. Patients possessing T. cruzi-specific IFN-γ-producing cells (i.e. IFN-γ producers) had higher levels of memory T cells capable of modulating the alpha chain of IL-7R and an efficient response to IL-7 compared to that in patients lacking (i.e. IFN-γ nonproducers) parasite-specific T-cell responses. IFN-γ producers also showed low levels of soluble IL-7R, high basal expression of Bcl-2 in T cells and low basal frequencies of activated CD25+ T cells. Modulation of IL-7R was inversely associated with serum IL-6 levels and positively associated with serum IL-8 levels. Circulating IL-21 and IL-27 levels were not associated with the frequency of IFN-γ producing cells but were reduced in less severe clinical forms of the disease. In vitro stimulation of PBMCs with IL-7 or IL-27 enhanced IFN-γ production in IFN-γ producers but not in IFN-γ nonproducers.Conclusions/SignificanceAlterations of the IL-7/IL-7R axis and in the levels of inflammatory cytokines were linked to impaired T. cruzi-specific IFN-γ production. These alterations might be responsible of the process of immune exhaustion observed in chronic Chagas disease.

show abstract

“…Thymic output was quantified into two independent methods: as TREC measured in PBMC or as thymic emigrant counts in peripheral blood. The following three populations of cells emerging from thymus were analysed: CD127 + CD132 − , CD127 + CD132 + and CD127 − CD132 + , respectively on: naive (CD45 + CD3 + RO − RA + ) and memory (CD45 + CD3 + RO + RA + ) cells, CD45 + CD3 + CD4 + and on CD45 + CD3 + CD8 + cells according to the results published by Sasson et al . In brief, their results suggested that T cells exit the thymus as CD127 + CD132 − T cells called RTE.…”

Section: Methodsmentioning

confidence: 99%

“…As these RTE mature through antigen activation, they co‐express CD127 and CD132. The continuous antigenic activation results in ongoing activation and expansion of these CD127 + CD132 + cells, which progress to terminally differentiated CD127 − CD132 + T cells . Therefore, RTE can be described as CD127 + CD132 − T cells.…”

Section: Introductionmentioning

confidence: 99%

Thymic emigration patterns in patients with type 2 diabetes treated with metformin

Dworacki

Urazayev²,

Bekmukhambetov³

et al. 2015

Immunology

View full text Add to dashboard Cite

SummaryRecent data suggest that thymic output, which provides the naive T cells necessary for the normal functioning of T-cell-dependent immunosurveillance cellular immunity including anti-cancer protection, can be disturbed in the course of type 2 diabetes. Metformin, an anti-diabetic drug commonly confirmed as an agent with many potential anti-cancer activities, might be helpful in this immune correction. The profile of thymic output was evaluated in the current study on the basis of the signal-joint T-cell receptor excision circle (sjTREC) concentration in peripheral blood polymorphonuclear cells and thymic emigrant content in peripheral blood evaluated from CD127 and/or CD132 antigen expression.

show abstract

Progressive Activation of CD127+132− Recent Thymic Emigrants into Terminally Differentiated CD127−132+ T-Cells in HIV-1 Infection

Cited by 8 publications

References 38 publications

Perturbed T Cell IL-7 Receptor Signaling in Chronic Chagas Disease

Perturbed T Cell IL-7 Receptor Signaling in Chronic Chagas Disease

Trypanosoma cruzi-specific IFN-γ-producing cells in chronic Chagas disease associate with a functional IL-7/IL-7R axis

Thymic emigration patterns in patients with type 2 diabetes treated with metformin

Contact Info

Product

Resources

About