RESUMO
KLRG1+ CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against systemic pathogens. Upon secondary infection, these long-lived effector cells (LLECs) are incapable of forming other circulating KLRG1- memory subsets such as central and effector memory T cells. Thus, KLRG1+ memory T cells are frequently referred to as a terminally differentiated population that is relatively short lived. Here, we show that after viral infection of mice, effector cells derived from LLECs rapidly enter nonlymphoid tissues and reduce pathogen burden but are largely dependent on receiving antigen cues from vascular endothelial cells. Single-cell RNA sequencing reveals that secondary memory cells in nonlymphoid tissues arising from either KLRG1+ or KLRG1- memory precursors develop a similar resident memory transcriptional signature. Thus, although LLECs cannot differentiate into other circulating memory populations, they still retain the flexibility to enter tissues and establish residency.
Assuntos
Memória Imunológica , Lectinas Tipo C , Células T de Memória , Receptores Imunológicos , Animais , Feminino , Camundongos , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Lectinas Tipo C/imunologia , Células T de Memória/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Imunológicos/imunologiaRESUMO
By 2030, individuals 65 years of age or older will make up approximately 20% of the world's population1. Older individuals are at the highest risk for mortality from infections, largely due to the pro-inflammatory, dysfunctional immune response, which is collectively known as immunosenescence2. During aging, CD8+ T cells acquire an exhausted phenotype, including increased expression of inhibitory receptors, such as programmed cell death 1 (PD1), a decline in effector function and elevated expression of inflammatory factors3-7. PD1 reduces T cell receptor activity via SHP2-dependent dephosphorylation of multiple pathways; accordingly, inhibiting PD1 activity through monoclonal antibodies increases CD8+ T cell effector response in young mice8-11. Attempts to improve CD8+ T cell responses by blocking inhibitory receptors are attractive; however, they can lead to adverse immune events due to overamplification of T cell receptor signaling and T cell activation12,13. Here we investigated the effect of monoclonal anti-PD1 immunotherapy during normal microbial experience, otherwise known as exposure to dirty mice, to determine whether it either improves exhausted CD8+ T cell responses in old mice or leads to a heightened inflammatory response and increased mortality.
Assuntos
Linfócitos T CD8-Positivos , Inflamação , Receptor de Morte Celular Programada 1 , Animais , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Inflamação/imunologia , Camundongos Endogâmicos C57BL , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Feminino , Envelhecimento/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêuticoRESUMO
Health disparities persist among Black men, notably in the context of lung cancer and stress-related health outcomes. This study explores these disparities through a community-based participatory research (CBPR) approach, citizen science, and social network theory, leveraging the expertise and trust of Black barbers as community leaders. The purpose is to understand the nuanced connections between stress and lung cancer in this demographic. Engaging 161 Black men across four Chicago neighborhoods, the study successfully collected hair samples and survey data, emphasizing the importance of culturally sensitive recruitment strategies. Findings highlight the effectiveness of the collaboration, showcasing the role of barbershops as community hubs for research. The study concludes by advocating for sustained partnerships with community leaders, emphasizing transparency in research communication, and promoting culturally grounded approaches to address health disparities and enhance research participation among underrepresented populations.