title: 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-7Rα 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.
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.
authors: João Luiz
authors: JL
authors: Silva-Filho
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.|Instituto Nacional de Ciência e Tecnologia em Biologia e Bioimagem, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Rio de Janeiro, 21941-902, Brazil.
authors: Celso
authors: C
authors: Caruso-Neves
authors: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil.|Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Rio de Janeiro, 21941-902, Brazil.
authors: Ana Acacia Sá
authors: AA
authors: Pinheiro
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D007114:Immunization; D016056:Immunodominant Epitopes / Q000235:genetics; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology / Q000472:pathogenicity
chemical_list: D016056:Immunodominant Epitopes; C110366:OVA-8; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D010047:Ovalbumin