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.


CONCLUSIONS
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.
INSERM U955, E10, Université Paris-Est, Créteil, France.
Hua
H
Liao
Emilie
E
Franck
Manuel
M
Fréret
Sahil
S
Adriouch
Yasmine
Y
Baba-Amer
Francois-Jerome
FJ
Authier
Olivier
O
Boyer
Romain K
RK
Gherardi
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000293:injuries* / Q000378:metabolism