Studies of ex vivo activated and expanded CD8+ NK-T cells in humans and mice.
Adoptive cellular therapy holds promise for improving the outcome of hematopoietic cell transplantation (HCT). At present, donor lymphocyte infusion post-HCT is efficacious for only a limited number of diseases, yet can induce significant graft versus host disease (GVHD). To improve the outcome of this approach, it would be beneficial to identify populations of T cells that retain graft versus tumor (GVT) effects with reduced propensity for GVHD. Here we describe studies of both human and murine expanded CIK cells or CD8+ NK-T cells. These related populations of cells are ex vivo activated and expanded T cells that express both T and NK markers. They can be generated from patients with malignancies and mediate cytotoxicity against autologous hematopoietic malignancies. Recent work in murine models show that these cells mediate cytotoxicity by using a perforin-granzyme and not through Fas ligand. In allogeneic stem cell transplantation experiments, large numbers of expanded CD8+ NK-T cells could be transplanted across major histocompatibility barriers without causing severe GVHD and GVT effects were retained. We conclude that expanded CD8+ NK-T cells are a promising form of cellular therapy in the allogeneic setting.
Verneris
Michael R
MR
Division of Pediatric Hematology/Oncology, and Bone Marrow Transplantation, Stanford, California 94305, USA. Verneris@Stanford.edu
Baker
Jeanette
J
Edinger
Matthias
M
Negrin
Robert S
RS
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice