- Prof. Jean-Paul Soulillou, Principal Investigator
- Dr. Sophie Brouard, Research Associate
- Prof. Robert Lechler, Research Associate
- Dr. Fabien Sebille, Research Associate
- Ms. Annaïck Pallier, Research Associate
- Mr. Marc André Delsuc, Research Associate
- Dr. Jean-Christophe Dore, Research Associate
- Dr. Minnie Sarwal, Scientific Consultant
- Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France
- Vβ Transcriptome Regulation during Allograft Rejection and Tolerance
Organ transplantation allows patients with end-stage disease of a vital organ to recover a normal life. Immune recognition of foreign tissues remains the main obstacle to transplantation, which requires long-term immunosuppression. The initial alloimmune responses proceed through the usual pathway of immunity in which allopeptides are presented by self-MHC. However, an unusually high proportion of naive T cells also directly recognise foreign MHC. This “direct” recognition is supposed to play a major role in acute rejection early after grafting. Normal recognition (self-APC) is supposed to operate in chronic rejection.
Our programme deals with a global representation of TCR usages in direct indirect pathways in vitro and in vivo. So far, TCR biases were only studied through qualitative TCR alteration (Immunoscope) of the Vβ chain segment (CDR3) interacting with peptide/MHC. This is relevant for analysing TCR biases in the indirect but not for direct pathway where CDR3 may not be involved. In addition, in all cases, the possible relevance of qualitative alteration must benefit from the knowledge of the number of clones involved (i.e. reflected by the amount of mRNA).
For the first time, we propose another approach that links qualitative and quantitative parameters and allows a global vision of TCR alterations (TcLand) in which qualitative alterations of Vβ mRNA are corrected by the amount of altered mRNA assessed by quantitative PCR.
Our aims are threefold:
1. To optimise the method.
2. To revisit allorecognition in vitro, in “direct type” MLR where pure T cells are confronted with allogeneic APC, and in vivo during acute rejection of heart allograft in rat and in one established model of experimental tolerance induction.
3. To identify and purify cells that may be responsible for tolerance in rare cases of human recipients of organ transplants who accept their grafts in the absence of any immunosuppressive drugs.