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- Andersson, Jennie, 1978, et al.
(författare)
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Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.
- 2014
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Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 20:12, s. 1891-8
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity.
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- Cromvik, Julia, 1980, et al.
(författare)
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Eosinophils in the blood of hematopoietic stem cell transplanted patients are activated and have different molecular marker profiles in acute and chronic graft-versus-host disease.
- 2014
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Ingår i: Immunity, inflammation and disease. - : Wiley. - 2050-4527. ; 2:2, s. 99-113
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Tidskriftsartikel (refereegranskat)abstract
- While increased numbers of eosinophils may be detected in patients with graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, it is not known if eosinophils play a role in GVHD. The aims of this study were to determine: whether eosinophils are activated during GVHD; whether the patterns of activation are similar in acute and chronic GVHD; and the ways in which systemic corticosteroids affect eosinophils. Transplanted patients (n = 35) were investigated for eosinophil numbers and the expression levels of 16 eosinophilic cell surface markers using flow cytometry; all the eosinophil data were analyzed by the multivariate method OPLS-DA. Different patterns of molecule expression were observed on the eosinophils from patients with acute, chronic, and no GVHD, respectively. The molecules that provided the best discrimination between acute and chronic GVHD were: the activation marker CD9; adhesion molecules CD11c and CD18; chemokine receptor CCR3; and prostaglandin receptor CRTH2. Patients with acute or chronic GVHD who received systemic corticosteroid treatment showed down-regulation of the cell surface markers on their eosinophils, whereas corticosteroid treatment had no effect on the eosinophil phenotype in the patients without GVHD. In summary, eosinophils are activated in GVHD, display different activation profiles in acute and chronic GVHD, and are highly responsive to systemic corticosteroids.
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- Cromvik, Julia, 1980
(författare)
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Graft-versus-Host Disease: Eosinophils, Chimerism and Clinical Features in Patients Undergoing Allogeneic Hematopoietic Stem Cell or Multivisceral Transplantation
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Graft-versus-host disease (GVHD) is a potentially severe complication that may develop after allogeneic hematopoietic stem cell transplantation (HSCT). It can also occur after transplantation with isolated intestinal grafts or after multivisceral transplantation (MVTX). GVHD is difficult to diagnose. The aims of this thesis were to 1) investigate the potential of the eosinophilic granulocyte as an immunoregulatory cell and biomarker in GVHD, 2) determine the incidence, risk factors and clinical features of GVHD in MVTX, 3) evaluate the utility of lymphocyte chimerism analyses to predict overall survival and risk of GVHD after HSCT. In paper I, we used an in vitro model of GVHD to see if eosinophils could inhibit allogeneic T cell proliferation. In paper II, flow cytometry was used to examine patterns of surface receptors on blood eosinophils from transplanted patients +/- GVHD and +/- systemic glucocorticoids. Paper III is a retrospective epidemiological study of patients with acute GVHD after MVTX. In paper IV, the predictive capacity of chimerism analyses and impact of chimerism status on the duration of immunosuppression was evaluated. It was found that eosinophils can inhibit allogeneic T cell proliferation in vitro and that eosinophils in patients with acute and chronic GVHD have an activated phenotype, which is altered by systemic steroid therapy. Our conclusion is that the blood eosinophils are activated and have immunoregulatory capacity in GVHD, and might serve as a biomarker of GVHD. In MVTX, it was seen that a tumor diagnosis or neoadjuvant chemotherapy were possible risk factors for GVHD. Finally, chimerism analyses could not predict relapse, survival or GVHD after HSCT. However, patients with mixed chimerism or chronic GVHD had longer treatment time with cyclosporine A.
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