RESUMEN
Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells. CAR-expressing human natural killer (NK) cells robustly and discriminately eliminated PD-1high follicular human T cells in vitro and in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1low T cell subsets, including regulatory T cells. These results establish a strategy for specific targeting of PD-1high T cells that can be advanced as a clinical tool for the selective depletion of pathogenic follicular T cells or other PD-1high target cells in certain disease states.
Asunto(s)
Células Asesinas Naturales/trasplante , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Adulto , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Autoinmunidad/genética , Autoinmunidad/inmunología , Células Cultivadas , Niño , Preescolar , Drosophila melanogaster , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/fisiología , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Receptores Quiméricos de Antígenos/genética , Linfocitos T/metabolismoRESUMEN
[This corrects the article DOI: 10.1016/j.xcrm.2020.100003.].