Human allo-reactive CD4+ T cells as strong mediators of anti-tumor immunity in NOD/scid mice engrafted with human acute lymphoblastic leukemia.
Leukemia
; 26(2): 312-22, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-21860431
ABSTRACT
Adoptive immunotherapy with donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) may not only mediate Graft-versus-Leukemia (GvL) reactivity, but also induce Graft-versus-Host Disease (GvHD). As HLA-class II molecules are predominantly expressed on hematopoietic cells, CD4+ T cells may selectively mediate GvL reactivity without GvHD. Here, we assessed the capacity of human CD4+ T cells to act as sole mediators of GvL reactivity in a NOD/scid mouse model for human acute lymphoblastic leukemia and chronic myeloid leukemia in lymphoid blast crisis. Highly purified CD4+ DLI eradicated the leukemic cells. The anti-tumor immunity was mediated by a polyclonal CD4+ T cell response comprising cytokine-producing T-helper and cytolytic T-effector cells directed against the mismatched HLA-class II molecules of the patients. Furthermore, primary leukemic cells acquired an antigen-presenting cell (APC) phenotype in vivo after DLI, as well as in vitro after co-culture with leukemia-specific CD4+ T cells. In conclusion, our results show that CD4+ T cells can be strong mediators of anti-tumor immunity, and provide evidence that cross-talk between CD4+ T cells and leukemic cells is the basis for induction of leukemic cells with an APC phenotype. These data emphasize the clinical relevance of CD4+ T cell based immunotherapy as treatment modality for hematological malignancies after alloSCT.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Leucemia
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda