Angiotensin II type-1 receptor (AT₁R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8⁺ T cells.

ABSTRACT: Angiotensin II (Ang II) and its receptor AT₁ (AT₁R), an important effector axis of renin-angiotensin system (RAS), have been demonstrated to regulate T-cell responses. However, these studies characterized Ang II and AT₁R effects using pharmacological tools, which do not target only Ang II/AT₁R axis. The specific role of AT₁R expressed by antigen-specific CD8⁺ T cells is unknown. Then we immunized transgenic mice expressing a T-cell receptor specific for SIINFEKL epitope (OT-I mice) with sporozoites of the rodent malaria parasite Plasmodium berghei expressing the cytotoxic epitope SIINFEKL. Early priming events after immunization were not affected but the expansion and contraction of AT₁R-deficient (AT₁R^-/-) OT-I cells was decreased. Moreover, they seemed more activated, express higher levels of CTLA-4, PD-1, LAG-3, and have decreased functional capacity during the effector phase. Memory AT₁R^-/- OT-I cells exhibited higher IL-7R? expression, activation, and exhaustion phenotypes but less cytotoxic capacity. Importantly, AT₁R^-/- OT-I cells show better control of blood parasitemia burden and ameliorate mice survival during lethal disease induced by blood-stage malaria. Our study reveals that AT₁R in antigen-specific CD8⁺ T cells regulates expansion, differentiation, and function during effector and memory phases of the response against Plasmodium, which could apply to different infectious agents.

SUBMITTER: Silva-Filho JL 

PROVIDER: S-EPMC5080615 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature