Donor-Derived Regulatory T Cells Attenuate the Severity of Acute Graft-Versus-Host Disease after Cord Blood Transplantation

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Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a curative therapy for some types of hematological disorders. However, allo-PBSCT is commonly complicated with acute graft-versus-host disease (aGVHD), characterized by host tissues being attacked by the grafted donor lymphocytes due to disparities of human leukocyte antigen (HLA) between the donor and host. By contrast, cord blood transplantation (CBT) is typically associated with low-grade severity of aGVHD, but the underlying mechanisms remain unclear. Donor-derived CD4⁺ alloreactive T cells (ATs) are of a specific lymphocyte subset, which can be activated by the recipient’s HLA, and play a crucial role in the onset of aGVHD. In the present study, we aimed to explore the difference in the property of CD4⁺ ATs between cord blood (CB) and adult peripheral blood (APB). We thus found that CB and APB CD4⁺ ATs contained not only effector T cells (Teffs) that execute aGVHD, but also a distinct subset of FoxP3⁺ regulatory T cells (Tregs) that may alleviate aGVHD. Importantly, CB CD4⁺ ATs contained higher percentage of FoxP3⁺ Tregs, compared to APB CD4⁺ ATs (P < 0.001), while lower percentage of Teffs (Th1, Th2 and Th17 cells) was detected in CB CD4⁺ ATs (P < 0.05, P < 0.001 and P < 0.05, respectively). Our findings suggest that FoxP3⁺ Tregs in CB CD4⁺ ATs may contribute to attenuating the severity of aGVHD observed after CBT.