Polyclonal anti-human thymocyte globulins (ATG) have been recently shown to significantly reduce the incidence of graft versus host disease (GVHD) post allogeneic stem cell transplantation (HSCT) from both sibling and unrelated donors. Induction of regulatory T cells has been suggested as one of the possible mechanisms. The aim of current study was to further characterize the T cell populations induced by ATG treatment and to delineate the mechanisms involved in ATG-induced tolerance. Phenotypic characterization revealed a significant increase in the expression of FoxP3, GITR, CD95, PD-1 and ICOS as well as the complement inhibitory molecules CD55, CD58 and CD59 on CD4+CD25+ T cells upon ATG treatment. Addition of ATG-treated cells to autologous and allogeneic peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/anti-CD28 antibodies resulted in significant inhibition of proliferation. Moreover, T-cell activation and IFNγ secretion were reduced in the presence of ATG-induced Treg cells. The CD4+CD25+CD127-low Treg fraction sorted from ATG-treated culture demonstrated greater suppressive potency than negative fraction. Conditioned medium produced by ATG-treated but not IgG-treated cells contained TGFβ and suppressed T cell proliferation and activation in a TGFβ receptor-dependent manner. TGFβ receptor kinase inhibitor SB431542 interfered with the suppressive activity of ATG-primed cells, enabling partial rescue of proliferation and IFNγ secretion. Moreover, SB431542 prevented Treg phenotype induction upon ATG treatment. Altogether, our data reveal the role of TGFβ signaling in ATG-mediated immunosuppression and further support the use of ATG, a potent inducer of regulatory T cells, for prevention of GVHD post HSCT and potentially other therapeutic applications.
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http://dx.doi.org/10.18632/oncotarget.21797 | DOI Listing |
Food Funct
December 2024
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China.
Astaxanthin is a xanthophyll carotenoid which has been associated with a number of health-promoting effects, including anti-aging; however, the underlying mechanisms are not fully understood. In the present study, it was found that astaxanthin promoted the longevity of wild-type (N2) (). The lifespan-extending effect of astaxanthin was associated with a significant decrease of lipofuscin accumulation and the reduction of the age-related decline in spontaneous motility.
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December 2024
Universidade Federal de São Paulo, Brazil.
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View Article and Find Full Text PDFPsychol Health Med
December 2024
Department of Physical Therapy, Faculty of Health Sciences, Universidad San Jorge, Zaragoza, Spain.
Introduction: Post-acute COVID-19 patients who were discharged from hospitals during the epidemic faced significant challenges, not only physical sequelae, but also psychological distress, anxiety, and depression. It is already known that continued exercise improves psychosocial components, but few studies have explored the impact of multimodal rehabilitation programs, including therapeutic education, in this type of patient. There are no studies that explore the application of these programs through asynchronous telerehabilitation, which would open up new therapeutic windows.
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December 2024
Division of Endocrinology, Department of Pediatrics, University of Florida, Gainesville, FL, United States.
Introduction: The immune-mediated destruction of insulin-producing β-cells characterizes type 1 diabetes. Nevertheless, exocrine pancreatic enzymes, including amylase, lipase, and trypsin, are also significantly reduced in type 1 diabetes. With an immunotherapy now approved to treat early-stage type 1 diabetes, biomarkers to delineate response to treatment are needed.
View Article and Find Full Text PDFAust N Z J Psychiatry
December 2024
School of Medicine and Psychology, College of Health and Medicine, The Australian National University, Canberra, ACT, Australia.
Introduction: Psilocybin, a classical psychedelic, has been rescheduled for use in psilocybin-assisted psychotherapy for treatment-resistant depression in Australia. While evidence for its use is promising, understanding the associated risks is crucial. Accordingly, this review aims to collate adverse event data from psilocybin-assisted psychotherapy clinical trials and evaluate its definition, way of measurement and reporting.
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