Pathogenic Role for {gamma}{delta} T Cells in Autoimmune Anti-Myeloperoxidase Glomerulonephritis [AUTOIMMUNITY]

Myeloperoxidase (MPO) anti-neutrophil cytoplasmic Ab (ANCA)–associated vasculitis results from autoimmunity to MPO. IL-17A plays a critical role in generating this form of autoimmune injury but its cell of origin is uncertain. We addressed the hypothesis that IL-17A–producing T cells are a nonredundant requisite in the development of MPO autoimmunity and glomerulonephritis (GN). We studied MPO-ANCA GN in wild type, αβ, or T cell–deficient (C57BL/6, βTCR^–/–, and TCR^–/– respectively) mice. Both T cell populations played important roles in the generation of autoimmunity to MPO and GN. Humoral autoimmunity was dependent on intact αβ T cells but was unaffected by T cell deletion. Following MPO immunization, activated T cells migrate to draining lymph nodes. Studies in TCR^–/– and transfer of T cells to TCR^–/– mice show that T cells facilitate the generation of anti-MPO autoimmunity and GN. TCR^–/– mice that received IL-17A^–/– T cells demonstrate that the development of anti-MPO autoimmunity and GN are dependent on T cell IL-17A production. Finally, transfer of anti-MPO CD4⁺ T cell clones to naive TCR^–/– and wild type mice with planted glomerular MPO shows that T cells are also necessary for recruitment of anti-MPO αβ CD4⁺ effector T cells. This study demonstrates that IL-17A produced by T cells plays a critical role in the pathogenesis of MPO-ANCA GN by promoting the development of MPO-specific αβ T cells.

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