Year-end Sale % OFF 
Abstract
In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα+ in small intestine expends in situ in response to changes in microbial flora.
Highlights
The intraepithelial layer of a small intestine is inhabited by several subsets of TCRαβ+ intraepithelial T cells (IELs) with different expression profiles of CD4 and CD8 co-receptors, mostly unknown antigen specificities, function, and diverse origin[1]
Clonal diversity of αβTCRs on IELs in the small intestine is shaped by unknown self, diet and microbial antigens presented in the context of classical and non-classical MHC molecules[16]
In the lymph nodes and spleen, most cytotoxic T cells represented conventional CD8αβ+ lineage, in both strains a small subset of the TCRαβCD8αα+ IELs was spotted in their spleens (Fig. 1A)
Summary
The intraepithelial layer of a small intestine is inhabited by several subsets of TCRαβ+ IELs with different expression profiles of CD4 and CD8 co-receptors, mostly unknown antigen specificities, function, and diverse origin[1]. It is anticipated that majority of TCRαβCD8αα+ IELs are thymus-derived, and this subset contribute to induction of tolerance to self-antigens, whereas peripherally-induced TCRαβCD8αα+ IELs co-express CD4 coreceptor and tend to recognize microbe-derived antigen(s) This notion is supported by the evidence that immature thymocytes from T cell receptor (TCR) transgenic mice differentiate to TCRαβ+CD8αα+ IELs when the former cells become exposed to a high dose of their cognate antigen[3,4]. We report that: 1/Direct comparison of αβTCRs expressed on DN thymocytes and TCRαβCD8αα+ IELs showed that no more than 50% of IELs expressed TCRs shared with their anticipated thymic precursors 2/Upon an introduction of new commensal(s) strains to GF TCRmini mice, both natural and induced TCRαβCD8αα+ IELs subsets responded by selective clonal expansions, 3/Introduction of a broad microbial flora resulted in increased similarity between intestinal CD4+ and both TCRαβCD8αα+ IELs subsets, which only in part depended on the presence of pTregs. Our results suggest that outside of the main, intrathymic pathway of TCRαβCD8αα+ IELs differentiation, mature CD4+ T cells can acquire CD8αα expression and downregulate the original co-receptor
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
