Artículos de revistas
Angiotensin Ii Type-1 Receptor (at(1)r) Regulates Expansion, Differentiation, And Functional Capacity Of Antigen-specific Cd8(+) T Cells
Registro en:
Scientific Reports. Nature Publishing Group, v. 6, p. , 2016.
2045-2322
WOS:000386175300001
10.1038/srep35997
Autor
Silva-Filho
Joao Luiz; Caruso-Neves
Celso; Sa Pinheiro
Ana Acacia
Institución
Resumen
Angiotensin II (Ang II) and its receptor AT(1) (AT(1)R), an important effector axis of renin-angiotensin system (RAS), have been demonstrated to regulate T-cell responses. However, these studies characterized Ang II and AT(1)R effects using pharmacological tools, which do not target only Ang II/AT(1)R axis. The specific role of AT(1)R 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 AT(1)R-deficient (AT(1)R-/-) 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 AT(1)R-/-OT-I cells exhibited higher IL-7Ra expression, activation, and exhaustion phenotypes but less cytotoxic capacity. Importantly, AT(1)R-/-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 AT(1)R in anti-genspecific 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. 6