Virus-infected mast cells activate virus-specific CD8+ T cells

Abstract

Efficient anti-viral responses of CD8⁺ T cells require signals that promote their effector cell differentiation, that are mainly provided by dendritic cells (DCs). Mast cells (MCs) are key drivers of DC maturation, but also influence their migration and antigen presenting properties and therefore indirectly mediate CD8⁺ T cell activation. MCs initiate innate immune responses at pathogen entry sites, promote the development of adaptive immune responses after infection, and release mediators including chemokines that recruit and activate immune cells including T cells during viral infections. However, whether MCs can directly activate virus-specific CD8⁺ T cells remains largely unknown. Here, we used an in vitro viral infection model with lymphocytic choriomeningitis virus (LCMV)-infected MCs or DCs co-cultured with either LCMV-specific CD8⁺ T cells or with WT (unspecific) CD8⁺ T cells. Similar to LCMV-infected DCs, LCMV-infected MCs clustered with virus-specific CD8⁺ T cells and induced their activation and production of antiviral cytokines. In addition, the co-stimulatory molecules CD86 and OX40L, but not CD80, were upregulated on MCs and an increased production of IL-6 and type I interferons after LCMV infection was shown. Our findings suggest that MCs can promote CD8⁺ T cell activation during viral infections. MC-mediated CD8⁺ T cell activation might be especially important within infected tissues where direct cellular interaction can take place. A better understanding of anti-viral functions of MCs may help developing new strategies to better treat viral infections.

Keywords: CD8+ T cells; LCMV; dendritic cells; mast cells; viral infection.