Immune regulation and tolerance 2

Wednesday September 14, 2022 from 08:00 to 09:30

Room: C5

404.4 Expression of TNFR2 and CD29 define a highly suppressive subset of human CD8+ T regulatory cells

Award Winner

Céline Sérazin, France has been granted the TTS-SFT International Transplantation Science Mentee-Mentor Awards

Céline Sérazin, France

University of Nantes - CR2TI UMR1064

Abstract

Expression of TNFR2 and CD29 define a highly suppressive subset of human CD8+ T regulatory cells

Céline Sérazin1, Léa Flippe1, Mathias Streitz2, Stephan Schlickeiser2, Hans Dieter Volk2, Ignacio Anegon1, Laurent David1, Séverine Bézie1, Carole Guillonneau1.

1Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France; 2Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany

CD8+ regulatory T cells (Tregs) were the first suppressive cells reported in 1970, but they were put aside for years due to a lack of markers to properly define them. Our team demonstrated that CD8+ Tregs identified by low and/or negative expression of CD45RC, one of the isoforms of the CD45 molecule, show potent suppressive activity in vitro and in vivo, while cells expressing high levels of CD45RC do not. Herein, we addressed the heterogeneity within CD8+CD45RClow/- Tregs and identified new markers.

We performed single cell RNA-sequencing on more than 10000 non-stimulated CD8+CD45RClow/- Tregs of 3 healthy volunteers (HV) and a CD screen analysis of 360 membrane molecules on different cells subsets of 4 HV (CD8+CD45RChigh; non-stimulated, stimulated or expanded CD4+CD25highCD127low and CD8+CD45RClow/- Tregs). Using these technologies, we were able to characterize the transcriptomic heterogeneity at a single cell level and the proteomic heterogeneity from non-stimulated CD8+CD45RClow/- Tregs. We thus identified sub-populations of cells and one cluster of particular interest expressing critical markers and molecules involved in tolerance. Further work on two of these promising membrane markers, i.e., TNFR2 and CD29, using cell sorting and suppressive assays highlighted CD8+CD45RClow/-TNFR2+CD29low Tregs subset as the most suppressive subsets within CD8+CD45RClow/- Tregs. Here, we reveal the importance of the combination of TNFR2 and CD29 as highly specific membrane markers for human CD8+ Tregs and highlighted their potential roles as targets for treatments in tolerance. Other new promising markers identified in our study showed an interesting role in CD8+ Tregs function; their precise roles are still under investigation. To date, to our knowledge, this is the largest characterization study of human CD8+ Tregs, this huge data resource will help in the current revival of CD8+ Tregs in research.



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