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T-cell alloreactivity and transplantation outcome

a budding role for heterologous immunity?

van den Heuvel, Heleen; Heidt, Sebastiaan; Roelen, Dave L.; Claas, Frans H.J.

Current Opinion in Organ Transplantation: August 2015 - Volume 20 - Issue 4 - p 454–460
doi: 10.1097/MOT.0000000000000218
HISTOCOMPATIBILITY: Edited by Elaine F. Reed

Purpose of review Despite the association between alloreactive T cells and poor graft survival, the mechanisms behind T-cell-mediated rejection are still under investigation. In this review, we will discuss the latest insights into the impact of T-cell alloreactivity on solid organ transplantation and hematopoietic stem cell transplantation (HSCT), with special emphasis on the potential impact of heterologous immunity.

Recent findings A large part of the memory T-cell repertoire is induced upon virus infections, and evidence for a role of T-cell receptor cross-reactivity of virus-induced memory T cells against allogeneic human leukocyte antigen (HLA) is accumulating in experimental and clinical solid organ transplantation studies. In HSCT, strong alloreactive potential of naïve T cells causes concerns for graft-versus-host disease while additional HLA-DP matching is suggested to prevent CD4+ alloreactivity. Furthermore, virus-induced memory T cells hamper mixed chimerism induction, pointing once more towards a role for heterologous immunity.

Summary Both memory and naïve T cells contribute to the alloimmune response after transplantation. Monitoring for T-cell phenotypes could help predict rejection episodes and/or graft-versus-host disease, allowing timely intervention. Tailoring donor lymphocyte infusions and additional HLA matching could prevent strong alloreactivity in HSCT. Furthermore, the potential role of heterologous immunity in T-cell alloreactivity and transplantation is gaining interest.

Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands

Correspondence to Heleen van den Heuvel, Leiden University Medical Center, Department of Immunohaematology and Blood Transfusion, P.O. Box 9600, Leiden 2300RC, the Netherlands. Tel: +31 71 5263362; fax: +31 71 5216751; e-mail:

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