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

• Published in: Current research in translational medicine 2019-02, Vol.67 (1), p.1-7
• Main Authors: Varlet, P., Rogeau, S., Trauet, J., Demaret, J., Labalette, M.
• Format: Article
• Language: English
• Subjects: Blood Component Removal - methods; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Engineering - methods; Cells, Cultured; Donor Selection; Graft engineering; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Graft-versus-host disease; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - methods; Humans; Immunologic Memory; Immunomagnetic Separation - methods; Life Sciences; Lymphocyte Depletion - methods; Naïve T cells; Peripheral Blood Stem Cell Transplantation - adverse effects; Peripheral Blood Stem Cell Transplantation - methods; Peripheral Blood Stem Cells - cytology; Receptors, CCR7 - metabolism; Selective T cell depletion; T-Lymphocyte Subsets; Transplantation Immunology; Transplantation, Homologous
• ISSN: 2452-3186; 2452-3186
• DOI: 10.1016/j.retram.2018.11.002

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. We performed a two-step immunomagnetic depletion of CD4+ CCR7+ T cells from ten G-CSF-mobilized PBSC apheresis samples. 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. 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.