T-cell immunity in the experimental autoimmune vasculitis rat model

TL;DR

This study examines T-cell responses in a rat model of vasculitis and finds that Th17 and Th1 cells are involved in kidney damage, but blocking IL-17A alone does not help.

Contribution

The study identifies the role of MPO-specific Th17 and Th1 cells in renal vasculitis and suggests combined cytokine neutralization may be needed.

Findings

MPO-immunized rats developed vasculitis with peak Th17 and Th1 cells in the kidneys at week six.

MPO-specific Th1 and Th17 cells were detectable in immunized rats but not in controls.

Blocking IL-17A did not reduce vasculitis or anti-MPO immunity.

Abstract

ANCA-vasculitis (AAV) is a small-vessel vasculitis characterized by the presence of autoantibodies against proteinase-3 (PR3) or myeloperoxidase (MPO). The dynamics of the T-cell response within tissues is studied best in animal models. It was the aim to analyze the lesional T-cell dynamics in the experimental autoimmune vasculitis model.

Female Wistar Kyoto-rats were immunized with human MPO emulsified in complete Freund's adjuvant. Control animals received complete Freund's adjuvant without MPO. Selected groups received anti-IL17A treatment. Lesional T-cells from kidneys were assessed by flow cytometry (FACS), realtime polymerase chain reaction (PCR) and EliSpot.

All animals immunized with MPO developed signs of vasculitis. At week six, lung damage expressed as petechial bleeding score and renal damage quantified by albuminuria were highest. As analyzed by FACS, the fraction of renal Th17 cells peaked at week six in MPO rats equaling the proportion of Th1 cells. MPO-specific renal Th1 and Th17 cells were detectable by EliSpot at weeks four and six post-immunization in MPO-immunized rats being absent in control rats. Neutralization of IL-17A did not affect the development of humoral and cellular anti-MPO immunity. Likewise, pulmonary and renal vasculitis were not ameliorated.

In summary, the dynamics of the lesional T-cell response in the EAV model shows a major participation of MPO-specific Th17 and Th1 cells in renal vasculitis. Simple cytokine neutralization was not efficacious in this disease model so that combined neutralization approaches should be studied further.

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