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

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.

Keywords: CD4+CD25+ T cells; IBDV; Infectious bursal disease virus; TGFβ; bursa of Fabricius; immunosuppression; regulatory T cells.