CD134/CD137 dual costimulation-elicited IFN-γ maximizes effector T-cell function but limits Treg expansion.

ABSTRACT: T-cell tolerance to tumor antigens represents a major hurdle in generating tumor immunity. Combined administration of agonistic monoclonal antibodies (mAbs) to the costimulatory receptors CD134 plus CD137 can program T-cells responding to tolerogenic antigen to undergo expansion, and effector T-cell differentiation, and also elicits tumor immunity. Nevertheless, CD134 and CD137 agonists can also engage inhibitory immune components. To understand how immune stimulatory versus inhibitory components are regulated during CD134 plus CD137 dual costimulation (DCo), the current study utilized a model where DCo programs T-cells encountering a highly tolerogenic self-antigen to undergo effector differentiation. IFN-γ was found to have a pivotal role in maximizing the function of effector T-cells, w

SUBMITTER: St Rose MC 

PROVIDER: S-EPMC3570742 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature