RESUMEN
CD8 T cell memory offers critical antiviral protection, even in the absence of neutralizing antibodies. The paradigm is that CD8 T cell memory within the lung tissue consists of a mix of circulating TEM cells and non-circulating TRM cells. However, based on our analysis, the heterogeneity within the tissue is much higher, identifying TCM, TEM, TRM, and a multitude of populations which do not perfectly fit these classifications. Further interrogation of the populations shows that TRM cells that express CD49a, both with and without CD103, have increased and diverse effector potential compared with CD49a negative populations. These populations function as a one-man band, displaying antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targets in vitro with delayed kinetics compared with effector CD8 T cells. Together, this study establishes that CD49a defines multiple polyfunctional CD8 memory subsets after clearance of influenza infection, which act to eliminate virus in the absence of direct killing, recruit and mature innate immune cells, and destroy infected cells if the virus persists.
Asunto(s)
Alphainfluenzavirus/inmunología , Linfocitos T CD8-positivos/metabolismo , Memoria Inmunológica , Integrina alfa1/metabolismo , Pulmón/metabolismo , Células T de Memoria/metabolismo , Infecciones por Orthomyxoviridae/metabolismo , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Células Cultivadas , Quimiocinas/metabolismo , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Interacciones Huésped-Patógeno , Alphainfluenzavirus/patogenicidad , Cinética , Pulmón/inmunología , Pulmón/virología , Masculino , Células T de Memoria/inmunología , Células T de Memoria/virología , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , FenotipoRESUMEN
The PE and PPE protein family are unique to mycobacteria. Though the complete genome sequences for over 500 M. tuberculosis strains and mycobacterial species are available, few PE and PPE proteins have been structurally and functionally characterized. We have therefore used bioinformatics tools to characterize the structure and function of these proteins. We selected representative members of the PE and PPE protein family by phylogeny analysis and using structure-based sequence annotation identified ten well-characterized protein domains of known function. Some of these domains were observed to be common to all mycobacterial species and some were species specific.