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T lymphocytes and muscle condition act like seeds and soil in a murine polymyositis model
Naoko Okiyama1, Takahiko Sugihara, Takatoku Oida
1Tokyo Medical and Dental University, Japan.
Objective:
It has been reported that polymyositis (PM) is driven by CD8+ cytotoxic T lymphocytes. The C protein-induced myositis (CIM) model we have established is similar to PM in pathology except that it undergoes spontaneous remission. We undertook the present study to delineate the roles of innate and acquired immunity in myositis.
Methods:
C57BL/6 mice were immunized with recombinant C protein fragments together with Freund's complete adjuvant (CFA) and Toll-like receptor (TLR) ligands at hind leg footpads and tail bases. CIM mediated by adoptive transfer of T cells to naive mice was treated with cytokine antagonists.
Results:
Second immunization with C protein fragments revealed no induction of tolerance. Injection of CFA and TLR ligands at the hind leg footpads reinduced myositis in the same legs. Interestingly, initial myositis was observed only in the CFA-treated forelegs. Transfer of C protein fragment-specific T cells from mice with CIM induced myositis in CFA- and TLR ligand-treated legs of recipient mice. CFA treatment resulted in the recruitment of macrophages producing inflammatory cytokines. Induction of myositis was inhibited by blocking interleukin-1 receptor or tumor necrosis factor α.
Conclusion:
Myositis development requires activation of autoaggressive T cells and conditioning of muscle tissue. CIM regression is due to attenuation of local CFA-induced immune activation. These results are in accordance with a "seed and soil" model of disease development and might offer clues to decipher clinical aspects of PM.
