Center for Research in Transplantation and Immunology, France
Title: Antigen-specific Tregs in transplantation
The laboratory: The Center for Research in Transplantation and Immunology (CRTI) is a research unit (UMR 1064) dedicated to transplantation science and immunology since 1993 in Nantes. The CRTI (3,000 m2 of laboratory surface area and two animal facilities) currently comprises 179 people and is part of the “Institute of Transplantation-Urology-Nephrology (ITUN)” at Nantes University Hospital (CHU Nantes). Our main research areas are immunology, transplantation, Immune Mediated Inflammatory Disorders (IMIDs), regenerative medicine and genetics. Everyone in the lab speaks English and we hold our lab meetings in English.
A 2-year post-doctoral position (with possibility of extending this period) is open in the team 2 “Gene and cell engineering in tolerance and regenerative medicine” under the supervision of Dr. Carole Guillonneau, for a highly motivated and talented post-doctoral fellow.
The city of Nantes offers a culturally active, young and dynamic environment. Nantes has an international airport, is conveniently located within 45 min drive from some beautiful sea resorts located on the French Atlantic coast and 2 hours high-speed train from Paris. The organization “Chercheurs Etrangers à Nantes” can help you with all administrative paperwork regarding visas, residence/work permits, social security, accommodation, French courses… Please go and visit their website for foreign researchers settling in Nantes: www.nantes-chercheur.org/en/
The context: Regulatory T cells (Tregs) have been described as being capable of inducing tolerance to allogeneic organs, however, CD8+ Treg, while demonstrated as crucial in some diseases, have been put aside and their role and potential in tolerance remain unclear. We investigate both in rodent and human antigen-specific regulatory CD8+ T lymphocytes, their biology at a cellular and molecular level, their generation upon encounter with an antigen and their role in transplantation tolerance and autoimmunity. These aspects are particularly important in current transplantation since new immunosuppressive strategies are based on the generation of a donor-specific tolerance.
The objectives of this project are to use human donor-derived antigen to expand human CD8+ Tregs and generate tolerogenic human antigen-specific T cells, to characterize the cell product and to provide the proof of concept for clinical application using transplanted humanized NSG mice in comparison to polyclonal CD8+ Tregs. The second objective of this project will be to determine the potential of TCR-engineered CD8+ T cells for transplantation tolerance using the rat cardiac transplantation model and already available “tolerogenic” TCRs (Tol-TCRs).
With this project, we expect to develop new strategies of tolerance induction using CD8+ Tregs and to further determine the role of the TCR and MHC/peptide interaction in this process.
– Candidate’s profile:
The applicant should hold a PhD in immunology with good skills in molecular biology, cell culture and flow cytometry. In vivo experience with rodent models will be appreciated. Technological facilities are available for graft surgery in rat and in humanized NSG mice, rat transgenesis-platform, tetramer production and purification, mRNA sequencing. INSERM1064 has shared equipment and instrumentation: tissue culture rooms: FACS for analysis and sorting; QPCR machines…
Competitive salary and excellent work environment are offered. Please send CV, a cover letter and names of three references to: firstname.lastname@example.org
– Relevant publications:
1. Bézie S., Picarda E., Ossart J., Martinet B., Anegon I. and Guillonneau C. Compensatory regulatory networks between CD8 T, B and myeloid cells in organ transplantation tolerance. J. Immunol. 2015 Nov 9. pii: 1500473.
2. Bézie S., Picarda E., Ossart J., Tesson L., Usal C., Renaudin K., Anegon I. and Guillonneau C. Interleukin-34, a new Treg-specific cytokine mediator of transplant tolerance. J. Clin Invest. 2015, Oct 1;125(10):3952-64.
3. Picarda E., Bézie S., Venturi V., Echasserieau K., Meriau E., Renaudin K., Delhumeau A., Brouard S., Bernardeau K., Anegon I. and Guillonneau C.. MHC class II allo-peptide activates TCR-biased-CD8+ Tregs and suppresses organ rejection. J. Clin Invest., 2014. Jun 2;124(6):2497-512.
4. LI X.-L., Menoret S., Bezie S., Caron L., Chabannes D., Hill M., Halary F., Angin M., Heslan M., Usal C., Liang L., Guillonneau C., Le Mauff B., Cuturi M.-C., Josien R. and Anegon I. Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance. J. Immunol., 2010. 185(2):823-33.
5. Guillonneau C., Marcelo H., Hubert F.X., Chiffoleau E., Hervé C., Li X.-L., Heslan M., Usal C., Tesson L., Menoret S., Saoudi A., Le Mauff B., Josien R., Cuturi M.C. and Anegon I. CD40Ig treatment results in allograft acceptance mediated by CD8CD45RC T cells, IFN-gamma, and indoleamine 2,3-dioxygenase. J. Clin. Invest. 2007. 117(4):1096-106.