Broadly reactive human CD4+ T cells against Enterobacteriaceae are found in the naïve repertoire and are clonally expanded in the memory repertoire. Issue 3 (28th December 2020)

• Record Type: Journal Article
• Authors: Cassotta, Antonino; Goldstein, Jérémie D.; Durini, Greta; Jarrossay, David; Baggi Menozzi, Franca; Venditti, Mario; Russo, Alessandro; Falcone, Marco; Lanzavecchia, Antonio; Gagliardi, Maria Cristina; Latorre, Daniela; Sallusto, Federica
• Is Part Of: European journal of immunology. Volume 51:Issue 3(2021)
• Page Start: 648
• Page End: 661
• Publication Date: 2020-12-28
• Subjects: cross‐reactivity -- Enterobacteriaceae -- human memory T cells -- human naïve T cells -- Th1*/17; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048630
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Enterobacteriaceae are a large family of Gram‐negative bacteria that includes both commensals and opportunistic pathogens. The latter can cause severe nosocomial infections, with outbreaks of multi‐antibiotics resistant strains, thus being a major public health threat. In this study, we report that Enterobacteriaceae‐reactive memory Th cells were highly enriched in a CCR6 + CXCR3 + Th1*/17 cell subset and produced IFN‐γ, IL‐17A, and IL‐22. This T cell subset was severely reduced in septic patients with K. pneumoniae bloodstream infection who also selectively lacked circulating K. pneumonie ‐reactive T cells. By combining heterologous antigenic stimulation, single cell cloning and TCR Vβ sequencing, we demonstrate that a large fraction of memory Th cell clones was broadly cross‐reactive to several Enterobacteriaceae species. These cross‐reactive Th cell clones were expanded in vivo and a large fraction of them recognized the conserved outer membrane protein A antigen. Interestingly, Enterobacteriaceae broadly cross‐reactive T cells were also prominent among in vitro primed naïve T cells. Collectively, these data point to the existence of immunodominant T cell epitopes shared among different Enterobacteriaceae species and targeted by cross‐reactive T cells that are readily found in the pre‐immune repertoire and are clonally expanded in the memory repertoire. Abstract : By combining in vitro priming of naïve T cells and ex vivo analysis of memory T cells, we demonstrate that specific and broadly cross‐reactive CD4 + T cells against Enterobacteriaceae are present in the naïve pre‐immune repertoire and become dominant in the memory repertoire. Enterobacteriaceae‐reactive memory Th cells are highly enriched in a CCR6 + CXCR3 + Th1*/17 cell subset.