Abstract
CD8+ T cells that secrete proinflammatory cytokines play a central role in exacerbation of inflammation; however, a new subpopulation of CD8 regulatory T cells has recently been characterized. This study analyzes the prominent role of these different subpopulations in the development of graft-versus-host disease (GVHD). Samples from 8 healthy donors mobilized with Filgrastim® (G-CSF) and 18 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated by flow cytometry. Mobilization induced an increase in Tc1 (p < 0.01), Th1 (p < 0.001), Tc17 (p < 0.05), and CD8+IL-10+ cells (p < 0.05), showing that G-CSF induces both pro- and anti-inflammatory profiles. Donor-patient correlation revealed a trend (p = 0.06) toward the development of GVHD in patients who receive a high percentage of Tc1 cells. Patients with acute GVHD (aGVHD), either active or controlled, and patients without GVHD were evaluated; patients with active aGVHD had a higher percentage of Tc1 (p < 0.01) and Tc17 (p < 0.05) cells, as opposed to patients without GVHD in whom a higher percentage of CD8 Treg cells (p < 0.01) was found. These findings indicate that the increase in Tc1 and Tc17 cells is associated with GVHD development, while regulatory CD8 T cells might have a protective role in this disease. These tests can be used to monitor and control GVHD.
Highlights
Graft-versus-host disease (GVHD) is one of the major causes of mortality after allogeneic hematopoietic stem cell transplantation (HSCT); it is induced by the inflammatory immune response of donor cells against host tissues recognized as foreign
To detect whether mobilization with Granulocyte-colony stimulating factor (G-CSF) induces proinflammatory cytokines and/or cell death, the expression of IFNγ and IL-17 as inflammation markers was determined, while Bcl-2 and active caspase-3 were used to evaluate the viability of CD4+ and CD8+ cells
Tc17 cells increased in patients with active and controlled graft-versus-host disease (GVHD), compared to patients without GVHD, but this increase was evidenced only after polyclonal activation with PMA and ionomycin. These results suggest that Tc1 and Tc17 cells play a prominent role in GVHD
Summary
Graft-versus-host disease (GVHD) is one of the major causes of mortality after allogeneic hematopoietic stem cell transplantation (HSCT); it is induced by the inflammatory immune response of donor cells against host tissues recognized as foreign. It is usually referred to as acute GVHD (aGVHD) when damage appears within the first 100 days after allogeneic HSCT and the main organs involved are the skin, liver, and gastrointestinal tract. The development of this disease depends on diverse immunological characteristics of the patient and donor at the time of infusion [1,2,3]. A central aspect and a subject of evaluation in GVHD development is the role of cytokines. Th17-related cytokines (IL-17A and IL-17F) have been said to be prominent in solid organ rejection in murine models [6,7,8,9] and while their presence is not required for GVHD development, they contribute to exacerbation of this disease [8]
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