Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab |
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| Authors: | Katie Matthews ZiYi Lim Behdad Afzali Laurence Pearce Atiyeh Abdallah Shahram Kordasti Antonio Pagliuca Giovanna Lombardi J Alejandro Madrigal Ghulam J Mufti and Linda D Barber |
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| Institution: | 1 The Anthony Nolan Research Institute, Royal Free Hospital, London;;2 Department of Haematological Medicine, King’s College London Denmark Hill Campus, London and;3 Department of Nephrology and Transplantation, King’s College London Guys and St. Thomas’ Hospital, London, UK |
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| Abstract: | BackgroundA variety of immune pathways can lead to graft-versus-host disease. A better understanding of the type of immune response causing graft-versus-host disease in defined clinical hematopoietic stem cell transplant settings is required to inform development of methods for monitoring patients and providing them tailored care.Design and MethodsTwenty-five patients were recruited presenting with myeloid malignancies and treated with a reduced intensity conditioning transplant regimen with graft-versus-host disease prophylaxis comprising in vivo lymphocyte depletion with alemtuzumab and cyclosporin. A prospective study was performed of lymphocyte subset reconstitution in peripheral blood in relation to the incidence of graft-versus-host disease.ResultsAcute graft-versus-host disease was associated with significantly higher numbers of natural killer cells and donor-derived effector CD4 T cells (CD45RO+ CD27−) early (day 30) after transplantation (p=0.04 and p=0.02, respectively). This association was evident before the emergence of clinical pathology in six out of seven patients. Although numbers of regulatory CD4 T cells (CD25high Foxp3+) were similar at day 30 in all patients, a significant deficit in those who developed acute graft-versus-host disease was apparent relative to effector CD4 T cells (median of 41 effectors per regulatory cell compared to 12 to 1 for patients without graft-versus-host disease) (p=0.03). By day 180, a functional regulatory CD4 T-cell population had expanded significantly in patients who developed chronic graft-versus-host disease, reversing the imbalance (median of 3 effectors per regulatory cell compared to 9.6 to 1 for patients without graft-versus-host disease) (p=0.018) suggesting no overt absence of immune regulation in the late onset form of the disease.ConclusionsImbalance of effector and regulatory CD4 T cells is a signature of graft-versus-host disease in this transplantation protocol. |
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| Keywords: | graft-versus-host disease CD4 T cell alemtuzumab |
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