12 December 2016

About characterizing regulatory populations to develop cell therapy approaches in transplantation.

“The CESTI IHU has made it possible to strengthen the transferability between basic research in animal experimental models and the study of patients in clinical practice, but also the reverse,” says Elise Chiffoleau, an INSERM researcher and coordinator of the “Tolerance in the Models of small animals” program.

Nowadays, organ transplantation in humans enables the treatment of many diseases that are related to vital function deficits (heart, kidney, marrow …). However, long-term rejection risks remain difficult to control. Indeed, the graft, which does not belong to the “self”, is recognized as a foreign element by the immune system of the recipient, which will then work to destroy it.

One of the objectives of the CESTI IHU is to obtain a specific tolerance in the donor by ideally avoiding immunosuppressive treatments, which cause harmful side effects, or at least by limiting their doses. A better understanding of the immunological mechanisms involved in transplant tolerance is therefore a primary goal in transplantation.

Dr. Chiffoleau’s team is interested in the regulatory mechanisms that are involved in allograft tolerance in experimental animal models. In collaboration with Dr. Sophie Brouard, she corroborates her results with those observed in patients who are spontaneously tolerant to their graft. As part of the CESTI program, these two researchers were able to characterize a subpopulation of leukocytes that are called regulatory B lymphocytes, of which they showed accumulation in “transplant tolerant” patients, and, as proof of concept, their ability to induce tolerance in cell therapy in experimental animal models.

Thus, this research “from the bench to the clinic” but also inversely “from the clinic to the bench” has allowed the highlighting of key actors of the tolerance processes in transplantation, in order to consider, in the longer term, a clinical application by cell therapy .

These works were also the subject of two publications in two international peer-reviewed journals:

  • Chesneau, M., L. Michel, et al. (2015). “Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties.” J Am Soc Nephrol 26(10): 2588-2598.
  • Durand, J., V. Huchet, et al. (2015). “Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents.” J Immunol.