Total lymphoid irradiation for graft-versus-host disease protection.
OBJECTIVE
The immunosuppressive effects of total lymphoid irradiation (TLI) for protection against graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation have been studied for years in animal models. In preclinical models of bone marrow transplantation non-myeloablative TLI conditioning protects against GvHD by skewing host T-cell subsets to favor regulatory natural killer T cells that suppress GvHD by polarizing donor T cells towards secretion of non-inflammatory cytokines such as IL-4. These preclinical models have recently been adapted to human transplantation.


RESULTS
Patients receiving allogeneic hematopoietic cell transplantation for hematological malignancies conditioned with TLI and depletive T-cell antibodies showed sustained donor chimerism, a reduced incidence of acute GvHD yet retained anti-tumor activity. As in the preclinical models, the low incidence of GvHD is associated with increased IL-4 secretion by chimeric donor T cells.


CONCLUSIONS
This review summarizes the evolution of the preclinical TLI protocols and their recent translation to clinical trials, and discusses the mechanisms involved in protection from GvHD and the induction of tolerance following mixed chimerism.
Kohrt
Holbrook
H
Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, California 94305, USA.
Lowsky
Robert
R
D000818:Animals; D002986:Clinical Trials as Topic; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D015182:Lymphatic Irradiation; D055611:Natural Killer T-Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015847:Interleukin-4