Document Detail

Photochemotherapy induces a faster apoptosis of alloreactive activated T cells than of nonalloreactive resting T cells in graft versus host disease.
MedLine Citation:
PMID:  21268310     Owner:  NLM     Status:  In-Process    
BACKGROUND: Graft versus host disease (GvHD) is the main complication after hematopoietic stem-cell transplantation.Extracorporeal photochemotherapy (ECP) is a cell therapy currently used for the treatment of T-cell–mediated diseases and seems as a valuable second-line therapy for patients suffering from steroid-refractory acute or chronic GvHD. ECP induces the apoptosis of treated cells and is believed to elicit a specific immune regulation of alloreactive T cells through repeated apoptotic T-cell infusions. However, its mechanisms of action have not yet been elucidated. In GvHD,alloreactive but not non alloreactive T cells are continuously activated by their environment. We hypothesized that ECP has a differential apoptotic effect on activated compared with resting T cells.
METHOD: The ECP-induced apoptosis of resting and activated T cells from patients with chronic GvHD was assessed.The kinetic of apoptosis was also evaluated using several triggers of T-cell activation such as mitogenic or antigen specific activation. The influence of survival cytokines (interleukin-2, -7, and -15) was also evaluated.
RESULTS: Activated T cells from patients with chronic GvHD underwent apoptosis faster than resting T cells. This phenomenon was confirmed using mitogenic and antigen-specific activated T cells from healthy donors and cannot be delayed by protective cytokines.
CONCLUSIONS: ECP induces a faster apoptosis of alloreactive activated T cells than of non alloreactive resting T cells in GvHD and more generally of activated T cells than of resting T cells. These novel findings provide new insights about the ECP-induced specific control of pathogenic T cells in GvHD.
Dalil Hannani; Etienne Merlin; Françoise Gabert; David Laurin; François Deméocq; Laurence Chaperot; Justyna Kanold; Joel Plumas
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  90     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-01-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1232-8     Citation Subset:  IM    
INSERM, U823, Immunobiologie et Immunotherapie des Cancers,Grenoble, France.
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