%0 Journal Article
%T Clonally expanded 污汛 T cells protect against Staphylococcus aureus skin reinfection
%A Alexer A. Merleev
%A Alexra F. Freeman
%A Alina I. Marusina
%A Alyssa G. Ashbaugh
%A Bret L. Pinsker
%A Carly A. Dillen
%A Da B. Lee
%A Emanual Maverakis
%A Haiyun Liu
%A Joshua D. Milner
%A Larissa S. May
%A Lloyd S. Miller
%A Loren G. Miller
%A Mark C. Marchitto
%A Michael R. Yeaman
%A Nathan K. Archer
%A Orly N. Farber
%A Roger V. Ortines
%A Scott I. Simon
%A Shuting S. Cai
%A Steven K. Lee
%A Steven M. Holl
%A Yu Wang
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI96481
%X 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-1汕每deficient mice exhibited poor neutrophil recruitment and bacterial clearance during primary infection that was rescued during secondary S. aureus challenge. The 污汛 T cells from skin-draining LNs utilized compensatory T cell每intrinsic TLR2/MyD88 signaling to mediate rescue by trafficking and producing TNF and IFN-污, which restored neutrophil recruitment and promoted bacterial clearance. RNA-sequencing (RNA-seq) of the LNs revealed a clonotypic S. aureus每induced 污汛 T cell expansion with a complementarity-determining region 3 (CDR3) aa sequence identical to that of invariant V污5+ dendritic epidermal T cells. However, this T cell receptor 污 (TRG) aa sequence of the dominant CDR3 sequence was generated from multiple gene rearrangements of TRGV5 and TRGV6, indicating clonotypic expansion. TNF- and IFN-污每producing 污汛 T cells were also expanded in peripheral blood of IRAK4-deficient humans no longer predisposed to S. aureus skin infections. Thus, clonally expanded 污汛 T cells represent a mechanism for long-lasting immunity against recurrent S. aureus skin infections
%U https://www.jci.org/articles/view/96481