ABERRANT T CELL RESPONSES IN THE BONE MARROW MICROENVIRONMENT OF PATIENTS WITH POOR GRAFT FUNCTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
(Abstract release date: 05/18/17)
EHA Library. Kong Y. 06/24/17; 181736; S449
Assoc. Prof. Yuan Kong
Contributions
Contributions
Abstract
Abstract: S449
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 12:15 - 12:30
Location: Room N104
Background
Poor graft function (PGF) remains a life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), and the underlying mechanisms have not yet been elucidated. Considerable evidence from murine studies has demonstrated that effective hematopoiesis depends on the specific bone marrow (BM) microenvironment, where hematopoietic stem cells reside. In this regard, we previously reported that PGF patients had impaired BM endosteal and vascular microenvironment (BBMT 2013; BMT 2016; Oncotarget 2016; Blood 2016). Moreover, our pilot study found that both CD4+ and CD8+ T cells were polarized towards a type 1 immune response in the BM microenvironment of PGF patients (N=10) compared to those in matched good graft function (GGF) patients(N=20) (BBMT 2016). Nevertheless, whether abnormalities of T cell subsets in the BM immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains to be explored.
Aims
To compare the T cell subsets in the BM immune microenvironment, including Th1, Tc1, Th2, Tc2, Th17, Tc17 cells and Tregs, between patients with PT and GGF after allo-HSCT.
Methods
This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD). Th17, Tc17, Th1, Tc1, Th2, Tc2 cells, Tregs and their subsets were analyzed by flow cytometry. The study was approved by the Ethics Committee of Peking University People’s Hospital, and written informed consent was obtained from all the patients before study-entry in accordance with the Declaration of Helsinki.
Results
The demographic and clinical characteristics were similar between allo-HSCT patients with PGF and those with GGF. The percentages of Th1 (37% vs. 26.4%, P=0.0005) and Tc1 (52.4% vs. 19%, P<0.0001) cells were significantly higher in PGF patients than in GGF patients, whereas the percentages of Th2 (0.8% vs. 2.4%, P<0.0001) and Tc2 (0.5% vs. 1.1%, P<0.0001) cells were markedly lower in the PGF group than in the GGF group. PGF patients showed significantly greater Th1 cell/Th2 cell (31.6 vs. 10.8, P<0.0001) and Tc1 cell/Tc2 cell ratios (108.8 vs. 18.4, P<0.0001) than those for GGF patients. Moreover, a significantly higher proportion of stimulated CD4+ T cells that produced IL-17 (Th17) was found in the BM of PGF patients than in the BM of GGF patients and HD (3.7% vs. 1.6% vs. 1.1%, P<0.05), whereas the percentages of Tregs in PGF patients were comparable to those in GGF patients and HD, resulting in a dramatically elevated ratio of Th17 cells/Tregs in the BM of PGF patients relative to those in GGF patients (1.01 vs. 0.57, P=0.04).
Conclusion
The present study revealed that aberrant T cell responses in the BM immune microenvironment may be involved in the pathogenesis of PGF after allo-HSCT. These findings will facilitate the optimization of immune regulation strategies and improve the outcome of PGF patients post-allotransplant.
Session topic: 21. Stem cell transplantation - Experimental
Keyword(s): Allogeneic hematopoietic stem cell transplant, Microenvironment, Immune response, Bone Marrow Failure
Abstract: S449
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 12:15 - 12:30
Location: Room N104
Background
Poor graft function (PGF) remains a life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), and the underlying mechanisms have not yet been elucidated. Considerable evidence from murine studies has demonstrated that effective hematopoiesis depends on the specific bone marrow (BM) microenvironment, where hematopoietic stem cells reside. In this regard, we previously reported that PGF patients had impaired BM endosteal and vascular microenvironment (BBMT 2013; BMT 2016; Oncotarget 2016; Blood 2016). Moreover, our pilot study found that both CD4+ and CD8+ T cells were polarized towards a type 1 immune response in the BM microenvironment of PGF patients (N=10) compared to those in matched good graft function (GGF) patients(N=20) (BBMT 2016). Nevertheless, whether abnormalities of T cell subsets in the BM immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains to be explored.
Aims
To compare the T cell subsets in the BM immune microenvironment, including Th1, Tc1, Th2, Tc2, Th17, Tc17 cells and Tregs, between patients with PT and GGF after allo-HSCT.
Methods
This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD). Th17, Tc17, Th1, Tc1, Th2, Tc2 cells, Tregs and their subsets were analyzed by flow cytometry. The study was approved by the Ethics Committee of Peking University People’s Hospital, and written informed consent was obtained from all the patients before study-entry in accordance with the Declaration of Helsinki.
Results
The demographic and clinical characteristics were similar between allo-HSCT patients with PGF and those with GGF. The percentages of Th1 (37% vs. 26.4%, P=0.0005) and Tc1 (52.4% vs. 19%, P<0.0001) cells were significantly higher in PGF patients than in GGF patients, whereas the percentages of Th2 (0.8% vs. 2.4%, P<0.0001) and Tc2 (0.5% vs. 1.1%, P<0.0001) cells were markedly lower in the PGF group than in the GGF group. PGF patients showed significantly greater Th1 cell/Th2 cell (31.6 vs. 10.8, P<0.0001) and Tc1 cell/Tc2 cell ratios (108.8 vs. 18.4, P<0.0001) than those for GGF patients. Moreover, a significantly higher proportion of stimulated CD4+ T cells that produced IL-17 (Th17) was found in the BM of PGF patients than in the BM of GGF patients and HD (3.7% vs. 1.6% vs. 1.1%, P<0.05), whereas the percentages of Tregs in PGF patients were comparable to those in GGF patients and HD, resulting in a dramatically elevated ratio of Th17 cells/Tregs in the BM of PGF patients relative to those in GGF patients (1.01 vs. 0.57, P=0.04).
Conclusion
The present study revealed that aberrant T cell responses in the BM immune microenvironment may be involved in the pathogenesis of PGF after allo-HSCT. These findings will facilitate the optimization of immune regulation strategies and improve the outcome of PGF patients post-allotransplant.
Session topic: 21. Stem cell transplantation - Experimental
Keyword(s): Allogeneic hematopoietic stem cell transplant, Microenvironment, Immune response, Bone Marrow Failure
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