IL-10-Engineered Human CD4⁺ Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism.

ABSTRACT: T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4⁺ T cells into T regulatory type 1 (Tr1)-like (CD4^IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4^IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4^IL-10

SUBMITTER: Locafaro G 

PROVIDER: S-EPMC5628869 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature