CD4+TGFβ+ cells infiltrated the bursa of Fabricius following IBDV infection, and correlated with a delayed viral clearance, but did not correlate with disease severity, or immunosuppression

Salik Nazki*, Vishwanatha R A P Reddy, Nitin Kamble, Jean-Remy Sadeyen, Munir Iqbal, Shahriar Behboudi, Holly Shelton, Andrew J Broadbent*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)

Abstract

INTRODUCTION: Infectious Bursal Disease Virus (IBDV) causes immunosuppression in chickens. While B-cell destruction is the main cause of humoral immunosuppression, bursal T cells from IBDV-infected birds have been reported to inhibit the mitogenic response of splenocytes, indicating that some T cell subsets in the infected bursa have immunomodulatory activities. CD4+CD25+TGFβ+ cells have been recently described in chickens that have immunoregulatory properties and play a role in the pathogenesis of Marek's Disease Virus.

METHODS: To evaluate if CD4+CD25+TGFβ+ cells infiltrated the bursa of Fabricius (BF) following IBDV infection, and influenced the outcome of infection, birds were inoculated at either 2 days or 2 weeks of age with vaccine strain (228E), classic field strain (F52/70), or PBS (mock), and bursal cell populations were quantified by flow cytometry.

RESULTS: Both 228E and F52/70 led to atrophy of the BF, a significant reduction of Bu1+-B cells, and a significant increase in CD4+ and CD8α+ T cells in the BF, but only F52/70 caused suppression of immune responses to a test antigen in younger birds, and clinical signs in older birds. Virus was cleared from the BF more rapidly in younger birds than older birds. An infiltration of CD4+CD25+T cells into the BF, and elevated expression of bursal TGFβ-1+ mRNA was observed at all time points following infection, irrespective of the strain or age of the birds, but CD4+TGFβ+cells and CD4+CD25+TGFβ+ cells only appeared in the BF at 28 dpi in younger birds. In older birds, CD4+TGFβ+ cells and CD4+CD25+TGFβ+ cells were present at earlier time points, from 7dpi following 228E infection, and from 14 and 28 dpi following F52/70 infection, respectively.

DISCUSSION: Our data suggest that an earlier infiltration of CD4+TGFβ+ cells into the BF correlated with a delayed clearance of virus. However, the influx of CD4+TGFβ+ cells and CD4+CD25+TGFβ+ into the BF did not correlate with increased pathogenicity, or immunosuppression.

Original languageEnglish
Article number1197746
JournalFrontiers in Immunology
Volume14
DOIs
Publication statusPublished - 8 Sept 2023

Bibliographical note

Funding Information:
SN was supported by UKRI Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/T008806/1. The project was additionally supported by a BBSRC Institute Strategic Programme Grant to the Pirbright Institute (BBS/E/I/00007030, BBS/E/I/00007031, BBS/E/I/00007032, BBS/E/I/00007035, BBS/E/I/00007036). Acknowledgments

Publisher Copyright:
Copyright © 2023 Nazki, Reddy, Kamble, Sadeyen, Iqbal, Behboudi, Shelton and Broadbent.

Keywords

  • Animals
  • Bursa of Fabricius
  • Chickens
  • Immunosuppression Therapy
  • Infectious bursal disease virus
  • Transforming Growth Factor beta

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