title: CD62L- memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice.
abstract: A major challenge in allogeneic hematopoietic cell transplantation is how to transfer T-cell immunity without causing graft-versus-host disease (GVHD). Effector memory T cells (CD62L(-)) are a cell subset that can potentially address this challenge because they do not induce GVHD. Here, we investigated how CD62L(-) T cells contributed to phenotypic and functional T-cell reconstitution after transplantation. On transfer into allogeneic recipients, CD62L(-) T cells were activated and expressed multiple cytokines and cytotoxic molecules. CD62L(-) T cells were able to deplete host radioresistant T cells and facilitate hematopoietic engraftment, resulting in enhanced de novo T-cell regeneration. Enhanced functional immune reconstitution was demonstrated in CD62L(-) T-cell recipients using a tumor and an influenza virus challenge model. Even though CD62L(-) T cells are able to respond to alloantigens and deplete host radioresistant immune cells in GVHD recipients, alloreactive CD62L(-) T cells lost the reactivity over time and were eventually tolerant to alloantigens as a result of prolonged antigen exposure, suggesting a mechanism by which CD62L(-) T cells were able to eliminate host resistance without causing GVHD. These data further highlight the unique characteristics of CD62L(-) T cells and their potential applications in clinical hematopoietic cell transplantation.
authors.affiliation: Division of Cellular Therapy/BMT, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Brice E
authors.initials: BE
authors.lastname: Barefoot
authors.forename: Wenjian
authors.initials: W
authors.lastname: Mo
authors.forename: Divino
authors.initials: D
authors.lastname: Deoliveira
authors.forename: Jessica
authors.initials: J
authors.lastname: Son
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Cui
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramsburg
authors.forename: Benny J
authors.initials: BJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D007113:Immunity, Innate / Q000276:immunology; D016867:Immunocompromised Host / Q000276:immunology / Q000502:physiology; D007156:Immunologic Memory / Q000276:immunology*; D019041:L-Selectin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D019041:L-Selectin