Ex vivo selection of recipient-type alloantigen-specific CD4(+)CD25(+) immunoregulatory T cells for the control of graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation.
Allogeneic hematopoietic stem-cell transplantation (HSCT) is the treatment of choice for many malignant and nonmalignant hematologic disorders. Donor T cells present in the hematopoietic stem-cell transplant improve engraftment and immune reconstitution and contribute to the graft-versus-leukemia effect, but are also responsible for the life-threatening graft-versus-host disease (GVHD). CD4(+)CD25(+) immunoregulatory T cells, which play a pivotal role in preventing organ-specific diseases, can also modulate GVHD if administered in equal numbers of T cells at the time of grafting. In this article, the authors describe a procedure of ex vivo selection and expansion of regulatory T cells specific for recipient-type alloantigens. These expanded regulatory T cells controlled GVHD. Their therapeutic use in HSCT should allow specific suppression of the activation of donor alloreactive T cells involved in GVHD while preserving the beneficial effects of other T cells.
Trenado
Aurélie
A
Biologie et Thérapeutique des Pathologies Immunitaires, Hôpital Pitié-Salpêtrière, Paris, France.
Fisson
Sylvain
S
Braunberger
Eric
E
Klatzmann
David
D
Salomon
Benoît L
BL
Cohen
José L
JL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*; D006086:Graft vs Host Disease / Q000209:etiology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D014184:Transplantation, Homologous / Q000009:adverse effects*
D007519:Isoantigens; D015375:Receptors, Interleukin-2