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

Abstract

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 musclespecific 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-␥ (IFN␥), interleukin-2 (IL-2), IL-10, and transforming growth factor ␤1 (TGF␤1). Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases with distinct histopathologic features that suggest either humorally mediated processes, primarily targeting the microcirculation (in dermatomyositis) and myofibers (in autoimmune necrotizing myopathies), or CD8ϩ T cell-mediated and class I major histocompatibility complex (MHC)-restricted autoimmune attack of myofibers (in polymyositis and inclusion body myositis) (1). Pathophysiologic studies have mainly explored how muscle cells can participate in immune cell interactions in polymyositis (2). In this setting, myofibers strongly express class I MHC molecules at their surface (1) and are invaded by autoinvasive T cells (3) expressing perforin (4). Clonal expansions of T cells are found in muscle and blood (5-8), and autoinvasive T cells exhibit selective gene rearrangement of their T cell receptor (TCR) with restricted

Injury and Subsequent Regeneration of Muscles for Activation of Local Innate Immunity to Facilitate the Development and Relapse of Autoimmune Myositis in C57BL/6 Mice

“…Antibodies against C protein were detected in mice with CIM, although myositis‐specific antibodies, including anti–Jo‐1 antibodies, were not . Mechanical crushing of the muscles from mice expressing ovalbumin transgene in the muscles was shown to induce proliferation of preliminarily transferred ovalbumin‐specific CTLs within the lymphoid tissues . Thus, muscle injury can supply muscle antigens and activate muscle antigen–specific T cells.…”

Biopersistence and Brain Translocation of Aluminum Adjuvants of Vaccines

“…Specialized for antigen uptake, monocyte-derived inflammatory DCs have an immature phenotype in the muscle. However, they migrate to the lymph node T-cell paracortex upon contact with tissue debris or foreign material, and arrive there as mature cells expressing costimulatory molecules ( 10 ). Inflammatory DCs may be crucial for the alum adjuvant activity as assessed by selective depletion studies ( 11 ), but eosinophils also appear to play an important role ( 12 ).…”

A dystrophic muscle broadens the contribution and activation of immune cells reacting to rAAV gene transfer

“…In that sense, muscle injury activates CD8+ T cells to endogenous expressed antigens. 23 All these reasons could explain the particular importance of CD8+ T cells for transgene rejection in dystrophic muscle but not in normal conditions.…”