Introduction

AUTHOR=Nazki Salik , Reddy Vishwanatha R. A. P. , Kamble Nitin , Sadeyen Jean-Remy , Iqbal Munir , Behboudi Shahriar , Shelton Holly , Broadbent Andrew J. TITLE=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 JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1197746 DOI=10.3389/fimmu.2023.1197746 ISSN=1664-3224 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.