Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection.

J Clin Invest 2018 03 5;128(3):1026-1042. Epub 2018 Feb 5.

Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

The mechanisms that mediate durable protection against Staphylococcus aureus skin reinfections are unclear, as recurrences are common despite high antibody titers and memory T cells. Here, we developed a mouse model of S. aureus skin reinfection to investigate protective memory responses. In contrast with WT mice, IL-1β-deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The γδ T cells from skin-draining LNs utilized compensatory T cell-intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-γ, which restored neutrophil recruitment and promoted bacterial clearance. RNA-sequencing (RNA-seq) of the LNs revealed a clonotypic S. aureus-induced γδ T cell expansion with a complementarity-determining region 3 (CDR3) aa sequence identical to that of invariant Vγ5+ dendritic epidermal T cells. However, this T cell receptor γ (TRG) aa sequence of the dominant CDR3 sequence was generated from multiple gene rearrangements of TRGV5 and TRGV6, indicating clonotypic expansion. TNF- and IFN-γ-producing γδ T cells were also expanded in peripheral blood of IRAK4-deficient humans no longer predisposed to S. aureus skin infections. Thus, clonally expanded γδ T cells represent a mechanism for long-lasting immunity against recurrent S. aureus skin infections.

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Source
https://www.jci.org/articles/view/96481
Publisher Site
http://dx.doi.org/10.1172/JCI96481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824877PMC
March 2018
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References

(Supplied by CrossRef)
Where does a Staphylococcus aureus vaccine stand?
Fowler et al.
Clin Microbiol Infect 2014

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