|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, 15 February 2008, Vol. 111, No. 4, pp. 2476-2484. Prepublished online as a Blood First Edition Paper on November 28, 2007; DOI 10.1182/blood-2007-08-109678.
TRANSPLANTATION Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease1 Penn State Milton S. Hershey Medical Center, Department of Medicine, Hershey, PA; 2 Section of Medical Oncology and Department of Immunobiology; 3 Department of Laboratory Medicine, 4 Department of Pathology, and 5 Department of Dermatology, Yale University School of Medicine, New Haven, CT
Much of the efficacy of allogeneic hematopoietic stem cell transplantation (alloSCT) in curing hematologic malignancies is due to a graft-versus-leukemia (GVL) effect mediated by donor T cells that recognize recipient alloantigens on leukemic cells. Donor T cells are also important for reconstituting immunity in the recipient. Unfortunately, donor T cells can attack nonmalignant host tissues and cause graft-versus-host disease (GVHD). We previously reported that donor CD4+ effector memory T cells (TEMs) do not cause GVHD but transfer functional T-cell memory. In the present work, we demonstrate in an MHC-mismatched model that CD4+ TEMs (unprimed to recipient antigens) mediate GVL against clinically relevant mouse models of chronic phase and blast crisis chronic myelogenous leukemia, without causing GVHD. By creating gene-deficient leukemias and using perforin-deficient T cells, we demonstrate that direct cytolytic function is essential for TEM-mediated GVL, but that GVL is retained when killing via FasL, TNF-
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2008 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
, TRAIL, and perforin is individually impaired. However, TEM-mediated GVL was diminished when both FasL and perforin pathways were blocked. Taken together, our studies identify TEMs as a clinically applicable cell therapy for promoting GVL and immune reconstitution, particularly in MHC-mismatched haploidentical alloSCTs in which T cell–depleted allografts are commonly used to minimize GVHD. 
