Cargando…

Spatial transcriptomics demonstrates the role of CD4 T cells in effector CD8 T cell differentiation during chronic viral infection

CD4 T cell help is critical to sustain effector CD8 T cell responses during chronic infection, notably via T follicular helper (Tfh)-derived interleukin-21 (IL-21). Conversely, CD4 depletion results in severe CD8 T cell dysfunction and lifelong viremia despite CD4 T cell reemergence following transi...

Descripción completa

Detalles Bibliográficos
Autores principales: Topchyan, Paytsar, Zander, Ryan, Kasmani, Moujtaba Y., Nguyen, Christine, Brown, Ashley, Lin, Siying, Burns, Robert, Cui, Weiguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9792173/
https://www.ncbi.nlm.nih.gov/pubmed/36450262
http://dx.doi.org/10.1016/j.celrep.2022.111736
Descripción
Sumario:CD4 T cell help is critical to sustain effector CD8 T cell responses during chronic infection, notably via T follicular helper (Tfh)-derived interleukin-21 (IL-21). Conversely, CD4 depletion results in severe CD8 T cell dysfunction and lifelong viremia despite CD4 T cell reemergence following transient depletion. These observations suggest that repopulating CD4 subsets are functionally or numerically insufficient to orchestrate a robust CD8 response. We utilize spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) to investigate CD4 T cell heterogeneity under CD4-replete and -deplete conditions and explore cellular interactions during chronic infection. Although IL-21-producing Tfh cells repopulate following transient CD4 depletion, they are outnumbered by immunomodulatory CD4 T cells. Moreover, the splenic architecture appears perturbed, with decreases in white pulp regions, coinciding with germinal center losses. These disruptions in splenic architecture are associated with diminished Tfh and progenitor CD8 T cell colocalization, providing a potential mechanism for impaired progenitor-to-effector CD8 T cell differentiation during “un-helped” conditions.