CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell transplantations

Abstract

BackgroundCD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable.ResultsWe found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD.ConclusionsTreg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.

Prospective randomized and crossover comparison of two apheresis machines for peripheral blood stem cell collection: a multicenter study

“…Residual dimethyl sulfoxide (DMSO), contaminating cells other than PBSCs, and viability of PBSCs in collected products are associated with adverse effects in recipients . In addition, excessive donor immune cells are implicated in graft‐versus‐host disease in allotransplantations . Therefore, efficient collections of PBSCs with fewer risks are critical for both donors and recipients.…”

Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs

“…For STR-PCR, 20 STR markers (D18S1270, D12S391, D20S161, Amelo genin, D11S488, D14S608, D10S2325, D8S306, D9S304, D8S1179, D8S639, D19S253, D16S3253, D21S1437, FGA, D5S818, SE33, TH01, VWF, Penta E, D18S51) were ampli ed using a GeneAmp PCR System 9700 (Thermo Fisher Scienti c, Waltham, MA, USA) as described previously [3,16,17]. In-house SNP-qPCR was performed with the sets of primers and probes speci c for 5 SNPs (rs2385512, rs3769393, rs748235, rs1386718, rs12438539) [18], using a QuantStudio 3, followed by analysis with QuantStudio Design & Analysis Software v1.4.3 (Thermo Fisher Scienti c).…”

“…However, allo-HSCTs often show comorbidity or mortality due to relapse of the hematologic disease, infections, graft-versus-host disease (GVHD), and graft failure associated with graft rejection or poor graft function [1]. Su cient hematopoietic and immune reconstitution by replacement of recipient-derived cells with donor cells is critical for successful allo-HSCT [2,3].…”

A possible role of low regulatory T cells in anti-acetylcholine receptor antibody positive myasthenia gravis after bone marrow transplantation

“…Flow cytometric analyses were performed by using the patient’s peripheral blood because depletion of Tregs after HSCT has been reported to be valuable in predicting chronic GVHD severity [ 5 – 7 ]. The Treg population in the peripheral blood, defined as CD4 + CD25 high FOXP3 + cells, was 0.24% of the total lymphocytes (Fig.…”