Myoinjury transiently activates muscle antigen–specific CD8+ T cells in lymph nodes in a mouse model

Objective To investigate the influence of myoinjury on antigen presentation to T cells in draining lymph nodes (LNs). Methods Muscle crush was performed in mice injected with exogenous ovalbumin (OVA) and in transgenic SM‐OVA mice expressing OVA as a muscle‐specific self antigen. Antigen exposure and the resulting stimulation of T cell proliferation in draining LNs was assessed by transferring carboxyfluorescein succinimidyl ester (CFSE)–labeled OVA‐specific CD8+ and CD4+ T cells from OT‐I and OT‐II mice and by measuring the dilution of CFSE, which directly reflects their proliferation. The role of monocyte‐derived dendritic cells (DCs) in T cell priming was assessed using pharmacologic blockade of DC migration. Immunofluorescence was used to detect CD8+ T cells, inflammatory monocyte‐derived DCs, and type I major histocompatibility complex (MHC)–expressing myofibers in crushed muscle, and to assess expression of perforin, interferon‐γ (IFNγ), interleukin‐2 (IL‐2), IL‐10, and transforming growth factor β1 (TGFβ1). Results OVA injection into intact muscle induced strong proliferation of CD4+ and CD8+ T cells, indicating efficient exposure of soluble antigens in draining LNs. OVA‐specific CD8+ T cell proliferation in draining LNs of SM‐OVA mice required myoinjury and was unaffected by pharmacologic inhibition of monocyte‐derived DC migration. On day 7 postinjury, activated CD8+ T cells expressing perforin, IFNγ and IL‐2 were transiently detected in crushed muscle, and these cells were in close contact with class I MHC–positive regenerating myofibers. Beginning on day 7, the immunosuppressive cytokines IL‐10 and TGFβ1 were conspicuously expressed by CD11b+ cells, and CD8+ T cells rapidly disappeared from the healing muscle. Conclusion Myofiber damage induces an episode of muscle antigen–specific CD8+ T cell proliferation in draining LNs. Activated CD8+ T cells transiently infiltrate the injured muscle, with prompt control by immunosuppressive cues. Inadequate control might favor sustained autoimmune myositis.