PMID- 30665880 OWN - NLM STAT- MEDLINE DCOM- 20200331 LR - 20200331 IS - 2452-3186 (Electronic) IS - 2452-3186 (Linking) VI - 67 IP - 1 DP - 2019 Feb TI - Immunomagnetic selective donor-derived CD4(+)CCR7(+) T cell depletion procedure for peripheral blood stem cells graft. PG - 1-7 LID - S2452-3186(18)30055-2 [pii] LID - 10.1016/j.retram.2018.11.002 [doi] AB - 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(+) naive 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(+) naive 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. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Varlet, P AU - Varlet P AD - Institut d'Immunologie, CHRU Lille, France; Universite de Lille, Inserm U995, LIRIC, Lille, France. Electronic address: pauline.varlet@chru-lille.fr. FAU - Rogeau, S AU - Rogeau S AD - Institut d'Immunologie, CHRU Lille, France; Universite de Lille, Inserm U995, LIRIC, Lille, France. FAU - Trauet, J AU - Trauet J AD - Institut d'Immunologie, CHRU Lille, France; Universite de Lille, Inserm U995, LIRIC, Lille, France. FAU - Demaret, J AU - Demaret J AD - Institut d'Immunologie, CHRU Lille, France; Universite de Lille, Inserm U995, LIRIC, Lille, France. FAU - Labalette, M AU - Labalette M AD - Institut d'Immunologie, CHRU Lille, France; Universite de Lille, Inserm U995, LIRIC, Lille, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190119 PL - France TA - Curr Res Transl Med JT - Current research in translational medicine JID - 101681234 RN - 0 (CCR7 protein, human) RN - 0 (Receptors, CCR7) SB - IM MH - Blood Component Removal/methods MH - CD4-Positive T-Lymphocytes/*cytology/immunology/metabolism MH - Cell Engineering/methods MH - Cells, Cultured MH - *Donor Selection MH - Graft vs Host Disease/immunology/prevention & control MH - Hematologic Neoplasms/immunology/therapy MH - Hematopoietic Stem Cell Transplantation/methods MH - Humans MH - Immunologic Memory MH - *Immunomagnetic Separation/methods MH - Lymphocyte Depletion/*methods MH - Peripheral Blood Stem Cell Transplantation/adverse effects/*methods MH - Peripheral Blood Stem Cells/cytology MH - Receptors, CCR7/metabolism MH - Transplantation Immunology MH - Transplantation, Homologous OTO - NOTNLM OT - Graft engineering OT - Graft-versus-host disease OT - Naive T cells OT - Selective T cell depletion OT - T-Lymphocyte Subsets EDAT- 2019/01/23 06:00 MHDA- 2020/04/01 06:00 CRDT- 2019/01/23 06:00 PHST- 2018/10/15 00:00 [received] PHST- 2018/11/07 00:00 [revised] PHST- 2018/11/14 00:00 [accepted] PHST- 2019/01/23 06:00 [pubmed] PHST- 2020/04/01 06:00 [medline] PHST- 2019/01/23 06:00 [entrez] AID - S2452-3186(18)30055-2 [pii] AID - 10.1016/j.retram.2018.11.002 [doi] PST - ppublish SO - Curr Res Transl Med. 2019 Feb;67(1):1-7. doi: 10.1016/j.retram.2018.11.002. Epub 2019 Jan 19.