Increase of CCR7− CD45RA+ CD8 T cells (TEMRA) in chronic graft-versus-host disease

D’Asaro, Matilde; Dieli, Francesco; Caccamo, Nadia; Musso, Maurizio; Porretto, Ferdinando; Salerno, Alfredo

doi:10.1038/sj.leu.2404079

Cited by 38 publications

(28 citation statements)

References 9 publications

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“…Yamashita et al (26) described an enrichment of donor alloreactive effector memory CD4 ϩ T cells in transplanted patients. This notion is strengthened by previous findings of D'Asaro et al (25) showing selective increase in CD8 effector memory RA ϩ cells in patients with chronic GvHD, whereas central memory T cells were reduced (25). In agreement with this, we observed a similar (early) induction of CD4 effector memory T cells and a (late) induction of CD8 ϩ effector memory T-cell function in CCR7 deficient chimeras.…”

Section: Discussionsupporting

confidence: 93%

“…As specific memory T-cell subsets, most notably effector memory T cells, have been implicated in the pathobiology of GvHD (25,26), blood lymphocytes were analyzed for the presence of different memory T-cell subsets. Kinetics of these memory T-cell subsets displayed different patterns in WT control and CCR7 Ϫ/Ϫ chimeras.…”

Section: Altered Percentages Of Circulating Memory T-cell Subsets In mentioning

confidence: 99%

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Impaired Effector Memory T-Cell Regulation Facilitates Graft Versus Host Disease in CCR7-Deficient Bone Marrow Transplant Chimeras

Jager

Canté-Barrett²,

Bot³

et al. 2009

Transplantation

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Section: Discussionsupporting

confidence: 93%

Section: Altered Percentages Of Circulating Memory T-cell Subsets In mentioning

confidence: 99%

Impaired Effector Memory T-Cell Regulation Facilitates Graft Versus Host Disease in CCR7-Deficient Bone Marrow Transplant Chimeras

Jager

Canté-Barrett²,

Bot³

et al. 2009

Transplantation

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“…6A). IL-15 may contribute to the observed T EMRA CD8 þ T-cell accumulation since T EMRA cells can be generated from central memory cells by IL-15 [33]. MSCtreated patients showed a tendency (at dþ90) of higher levels of T EMRA CD8 þ T-cells; this reached statistical significance by dþ180 (Fig.…”

Section: Discussionmentioning

confidence: 49%

“…þ T EMRA cells have been associated with the development of chronic GVHD after allo-HSCT [33] (which was not confirmed in our limited patient cohort; data not shown). Remarkably, treatment with MSCs was associated with increased levels of IL-2 at all evaluated time points, whereas they were below normal in the control group (Fig.…”

Section: Discussionmentioning

confidence: 63%

Alterations in the Cellular Immune Compartment of Patients Treated with Third-Party Mesenchymal Stromal Cells Following Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2013

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Adoptive transfer of third-party mesenchymal stromal cells (MSCs) has emerged as a promising tool for the treatment of steroid-refractory graft-versus-host disease (GVHD). Despite numerous in vitro studies and preclinical models, little is known about their effects on the patients' immune system. We assessed immune alterations in the T-cell, B-cell, natural killer cell, dendritic cell, and monocytic compartments of steroid-refractory GVHD patients 30, 90, and 180 days after MSC (n = 6) or placebo (n = 5) infusion, respectively. Infused MSCs were bioactive as suggested by the significant reduction in epithelial cell death, which represents a biomarker for acute GVHD. There were several indications that MSCs shift the patients' immune system toward a more tolerogenic profile. Most importantly, infusion of MSCs was associated with increased levels of regulatory (forkhead box P3 (FOXP3)+ and interleukin (IL)-10+) T-cells, reduced pro-inflammatory IL-17+ T(Th17)-cells, and skewing toward type-2 T-helper cell responses. Furthermore, IL-2, which has been recently shown to exert a positive immune modulating effect in GVHD patients, was higher in the MSC patients at all evaluated time points during 6 months after MSC-infusion. Overall, our findings will contribute to the refinement of monitoring tools, for assessing MSC treatment-efficacy and increase our understanding regarding the MSCs' in vivo effects.

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“…Regarding other T-cell subpopulations, an increase in CCR7 − CD45RA + CD8 T-cells that are effector memory T-cells and a decrease of CCR7 + CD45RA + naïve T-cells as well as CCR7 + CD45RA − central memory T-cells has been reported in patients with cGvHD (30). The authors speculated whether their findings were the consequence of prolonged alloantigen exposure or interleukin-15 (IL-15) stimulation since patients with cGvHD reportedly have elevated IL-15 levels and effector memory T-cells can be generated by IL-15 stimulation.…”

Section: Cellular Biomarkersmentioning

confidence: 99%

B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2017

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main curative therapy for hematological malignancy such as leukemias, lymphomas, or multiple myelomas and some other hematological disorders. In this therapy, cure of hematological diseases relies on graft-versus-malignancy effects by allogenic immune cells. However, severe posttransplant treatment-associated complications such as acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) limit this approach. Most research into GvHD has concentrated on the aGvHD, while the more complex and multifaceted chronic form has been largely poorly investigated. cGvHD is a multi-organ autoimmune disorder and is the major cause of non-relapse morbidity and mortality following allo-HSCT, occurring in about 50% of patients, or 13,000–15,000 patients per year worldwide. Therefore, there is a high medical need for an early prediction of these therapy-associated toxicities. Biomarkers have gained importance over the last decade in diagnosis, in prognosis, and in prediction of pending diseases or side effects. Biomarkers can be cells, factors isolated from target tissues, or soluble factors that can be detected in body fluids. In this review, we aim to summarize some of the recent developments of biomarkers in the field of allo-HSCT. We will focus on cell-based biomarkers (B-cell subsets) for cGvHD and soluble factors including microRNA (miRNA), which are excreted into serum/plasma and urine. We also discuss the potential role of cytosolic and extracellular 70 kDa heat shock proteins (HSP70) as potential biomarkers for aGvHD and their role in preclinical models. Proteomic biomarkers in the blood have been used as predictors of treatment responses in patients with aGvHD for many years. More recently, miRNAs have been found to serve as a biomarker to diagnose aGvHD in the plasma. Another development relates to urine-based biomarkers that are usually detected by capillary electrophoresis and mass spectrometry. These biomarkers have the potential to predict the development of severe aGvHD (grades III–IV), overall mortality, and the pending development of cGvHD in patients posttransplant.

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Increase of CCR7− CD45RA+ CD8 T cells (TEMRA) in chronic graft-versus-host disease

Abstract: References1 Martinelli G, Terragna C, Zamagni E, Ronconi S, Tosi P, Lemoli RM et al. Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma.

Cited by 38 publications

References 9 publications

Impaired Effector Memory T-Cell Regulation Facilitates Graft Versus Host Disease in CCR7-Deficient Bone Marrow Transplant Chimeras

Impaired Effector Memory T-Cell Regulation Facilitates Graft Versus Host Disease in CCR7-Deficient Bone Marrow Transplant Chimeras

Alterations in the Cellular Immune Compartment of Patients Treated with Third-Party Mesenchymal Stromal Cells Following Allogeneic Hematopoietic Stem Cell Transplantation

B-Cell-Based and Soluble Biomarkers in Body Liquids for Predicting Acute/Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

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