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Mucosal Immunol ; 15(1): 176-187, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34462572

RESUMEN

Although murine γδ T cells are largely considered innate immune cells, they have recently been reported to form long-lived memory populations. Much remains unknown about the biology and specificity of memory γδ T cells. Here, we interrogated intestinal memory Vγ4 Vδ1 T cells generated after foodborne Listeria monocytogenes (Lm) infection to uncover an unanticipated complexity in the specificity of these cells. Deep TCR sequencing revealed that a subset of non-canonical Vδ1 clones are selected by Lm infection, consistent with antigen-specific clonal expansion. Ex vivo stimulations and in vivo heterologous challenge infections with diverse pathogenic bacteria revealed that Lm-elicited memory Vγ4 Vδ1 T cells are broadly reactive. The Vγ4 Vδ1 T cell recall response to Lm, Salmonella enterica serovar Typhimurium (STm) and Citrobacter rodentium was largely mediated by the γδTCR as internalizing the γδTCR prevented T cell expansion. Both broadly-reactive canonical and pathogen-selected non-canonical Vδ1 clones contributed to memory responses to Lm and STm. Interestingly, some non-canonical γδ T cell clones selected by Lm infection also responded after STm infection, suggesting some level of cross-reactivity. These findings underscore the promiscuous nature of memory γδ T cells and suggest that pathogen-elicited memory γδ T cells are potential targets for broad-spectrum anti-infective vaccines.


Asunto(s)
Infecciones Bacterianas/inmunología , Vacunas Bacterianas/inmunología , Citrobacter rodentium/fisiología , Listeria monocytogenes/fisiología , Células T de Memoria/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Salmonella typhi/fisiología , Animales , Antígenos Bacterianos/inmunología , Células Cultivadas , Reacciones Cruzadas , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunidad Heteróloga , Células T de Memoria/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Especificidad del Receptor de Antígeno de Linfocitos T
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