Clonal Vγ6 ⁺ Vδ4 ⁺ T cells promote IL-17–mediated immunity against <i>Staphylococcus aureus</i> skin infection

Abstract

T cell cytokines contribute to immunity against <i>Staphylococcus aureus</i>, but the predominant T cell subsets involved are unclear. In an <i>S. aureus</i> skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for <i>TRG</i> and <i>TRD</i> sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of <i>TRGV5</i> or <i>TRGV6</i> and <i>TRDV4</i> However, only <i>TRGV6</i> and <i>TRDV4</i> but not <i>TRGV5</i> sequences expanded. Finally, Vγ6⁺ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6⁺Vδ4⁺ T cells in immunity against <i>S. aureus</i> skin infections.