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Double-negative regulatory T cells induce allotolerance when expanded after allogeneic haematopoietic stem cell transplantation.

Abstract：

:Double-negative (DN) regulatory T cells (Tregs) are specialized T lymphocytes involved in the down-modulation of immune responses, resulting in allotolerance after allogeneic haematopoietic stem cell transplantation (HSCT). Most of the properties of DN Tregs were identified in murine models, including the unique ability to suppress alloreactive syngeneic effector T cells in an antigen-specific manner via Fas/Fas-ligand interactions. We investigated the behaviour of DN Tregs following human allogeneic HSCT with regard to occurrence of graft-versus-host disease (GvHD) and restoration of T-cell receptor repertoire in a cohort of 40 patients. The frequency of DN Tregs and CD4/CD8 TCR repertoire was measured serially and at the time of diagnosis of GvHD by flow cytometry. Analysis demonstrated a positive correlation between degree of alloreactivity, as measured by grade of GvHD, and the number of variable beta chain (Vbeta) family expansions in both T-cell populations. We also found that a deficiency of DN Tregs was associated with an increased number of Vbeta family expansions, and most importantly, with the occurrence of GvHD. All individuals who demonstrated more than 1% DN Tregs did not develop GvHD, providing evidence that DN Tregs participate in peripheral tolerance to prevent GvHD when expanded after allogeneic HSCT.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

McIver Z,Serio B,Dunbar A,O'Keefe CL,Powers J,Wlodarski M,Jin T,Sobecks R,Bolwell B,Maciejewski JP

doi

10.1111/j.1365-2141.2008.07021.x

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

170-8

issue

2

eissn

0007-1048

issn

1365-2141

pii

BJH7021

journal_volume

141

pub_type

杂志文章

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