A Fixed Spatial Structure of CD8+ T Cells in Tissue during Chronic HSV-2 Infection.
J Immunol
; 201(5): 1522-1535, 2018 09 01.
Article
en En
| MEDLINE
| ID: mdl-30045971
ABSTRACT
Tissue-resident CD8+ T cells (Trm) can rapidly eliminate virally infected cells, but their heterogeneous spatial distribution may leave gaps in protection within tissues. Although Trm patrol prior sites of viral replication, murine studies suggest they do not redistribute to adjacent uninfected sites to provide wider protection. We perform mathematical modeling of HSV-2 shedding in Homo sapiens and predict that infection does not induce enough Trm in many genital tract regions to eliminate shedding; a strict spatial distribution pattern of mucosal CD8+ T cell density is maintained throughout chronic infection, and trafficking of Trm across wide genital tract areas is unlikely. These predictions are confirmed with spatial analysis of CD8+ T cell distribution in histopathologic specimens from human genital biopsies. Further simulations predict that the key mechanistic correlate of protection following therapeutic HSV-2 vaccination would be an increase in total Trm rather than spatial reassortment of these cells. The fixed spatial structure of Trm induced by HSV-2 is sufficient for rapid elimination of infected cells but only in a portion of genital tract microregions.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Herpes Genital
/
Esparcimiento de Virus
/
Herpesvirus Humano 2
/
Modelos Inmunológicos
/
Linfocitos T CD8-positivos
/
Memoria Inmunológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2018
Tipo del documento:
Article