Immunomagnetic selective donor-derived CD4+CCR7+ T cell depletion procedure for peripheral blood stem cells graft.

Abstract:

PURPOSE OF THE STUDY:While acute graft-versus-host-disease (GVHD) is a T cell-mediated disease caused by alloreactive donor T cells, we and others have highlighted that patients who received higher proportion of donor CD4+ naïve and central memory T cells expressing the chemokine receptor 7 (CCR7) more often developed acute GVHD than those who did not. Consequently, we then investigated in vitro the impact of selective CD4+ CCR7+ T cell depletion on immune reactions and showed that such a depletion reduced alloreactivity without altering acquired anti-infectious reactions. In order to translate these findings to clinic, we now developed a compliant procedure for a selective reduction of the CD4+ naïve and central memory T cell subset relevant to peripheral blood stem cell (PBSC) allografts. PATIENTS AND METHODS:We performed a two-step immunomagnetic depletion of CD4+ CCR7+ T cells from ten G-CSF-mobilized PBSC apheresis samples. RESULTS:A median of 89% (82-94%) of CD4+ CCR7+ T cells could be depleted. This allowed a marked reduction of the alloreactive immune response against allogenic dendritic cells compared with unmanipulated cells. The preservation of CD34+ cell number and the hematopoietic progenitor function were controlled. Functional tests showed that the selection procedure did not interfere with the capacity of pathogen-specific T cells to produce interferon-gamma in response to certain viral pathogens. CONCLUSION:Our results pave the way to a feasible procedure that can be used in patients undergoing allo-hematopoietic cell transplantation and particularly for improving haploidentical transplant results by controlling GVHD, the main immune complication.

journal_name

Curr Res Transl Med

authors

Varlet P,Rogeau S,Trauet J,Demaret J,Labalette M

doi

10.1016/j.retram.2018.11.002

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

1-7

issue

1

issn

2452-3186

pii

S2452-3186(18)30055-2

journal_volume

67

pub_type

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