Differential sensitivity of T lymphocytes and hematopoietic precursor cells to photochemotherapy with 8-methoxypsoralen and ultraviolet A light.
The combination of 8-methoxypsoralen (8-MOP) and long wave ultraviolet radiation (UV-A) has immunomodulatory effects and might abolish both graft-vs-host and host-vs-graft reactions after allogeneic hematopoietic stem cell transplantation. In the present study, we have confirmed the sensitivity of T lymphocytes to 8-MOP treatment plus UV-A exposure as evidenced by the abrogation of the alloreactivity in mixed lymphocyte cultures as well as the inhibition of the response to phytohemagglutinin A. However, the clonogenic capacity of the bone marrow hematopoietic progenitors was inhibited with UV-A doses lower than the doses needed to inhibit T-lymphocytes alloreactivity. Moreover, long-term bone marrow cultures showed that 8-MOP plus UV-A treatment had detrimental effects on the more immature bone marrow stem cells. These data were confirmed when murine bone marrow graft was treated with 8-MOP, exposed to UV-A, then transplanted into semiallogeneic recipient mice. The treated cells could not maintain their clonogenic capacity in vivo resulting in death of all animals. Taken together, these data show that ex vivo 8-MOP plus UV-A treatment of the marrow graft cannot be used to prevent post-bone marrow transplantation alloreactivity.
Mabed
Mohamed
M
Hematology and Medical Oncology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt. mohmabed@mans.edu.eg
Coffe
Christian
C
Racadot
Evelyne
E
Angonin
Regis
R
Pavey
Jean-Jaques
JJ
Tiberghien
Pierre
P
Herve
Patrick
P
D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006087:Graft vs Host Reaction / Q000187:drug effects / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006789:Host vs Graft Reaction / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008730:Methoxsalen / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D011701:PUVA Therapy / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism; D014184:Transplantation, Homologous; D014466:Ultraviolet Rays
D008730:Methoxsalen