IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts

Hengcheng Zhang, Cecilia B. Cavazzoni, Manuel A. Podestà, Elsa D. Bechu, Garyfallia Ralli, Pragya Chandrakar, Jeong Mi Lee, Ismail Sayin, Stefan G. Tullius, Reza Abdi, Anita S. Chong, Bruce R. Blazar, Peter T. Sage

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins, and functions of Tfh cells in this process have not been fully characterized. Here we show that a subset of effector Tfh cells marked by previous IL-21 production is potently induced during allogeneic kidney transplantation and is inhibited by immunosuppressive agents. Single-cell RNA-Seq revealed that these lymph node (LN) effector Tfh cells have transcriptional and clonal overlap with IL-21–producing kidney-infiltrating Tfh cells, implicating common origins and developmental trajectories. To investigate the precise functions of IL-21–producing effector Tfh cells in LNs and allografts, we used a mouse model to selectively eliminate these cells and assessed allogeneic B cell clonal dynamics using a single B cell culture system. We found that IL-21–producing effector Tfh cells were essential for transplant rejection by regulating donor-specific germinal center B cell clonal dynamics both systemically in the draining LN and locally within kidney grafts. Thus, IL-21–producing effector Tfh cells have multifaceted roles in Ab-mediated rejection after kidney transplantation by promoting B cell alloimmunity.

Original languageEnglish (US)
Article numbere169793
JournalJCI Insight
Volume8
Issue number20
DOIs
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023, Zhang et al.

PubMed: MeSH publication types

  • Journal Article

Fingerprint

Dive into the research topics of 'IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts'. Together they form a unique fingerprint.

Cite this