Les cytokines homéostatiques, IL-7 et IL-15, au cours de l'allogreffe de CSH : leurs évolutions selon le conditionnement et leurs valeurs prédictives de la GVH aiguë et de la rechute

My PhD was realised in the research team EA2686 at the Pole of Immunology in the Center of Biology Pathology of Lille under the direction of Doctor Myriam Labalette and in collaboration with Professor Ibrahim Yakoub-Agha from the department of Blood Diseases in the Hospital of Lille. The central line of the my work concern the implication of the different subpopulations of naive and memory T cells in the immune reconstitution and the main events post allograft of hematopoietic stem cells (HSC). 1)Study of factors controlling the homeostatic proliferation of T cells after allograft : By a prospective study, our team showed that the dynamic of reconstitution of subpopulations of naive and memory T cells during the immune reconstitution after allograft of HSC affects the occurrence of late events (Yakoub-Agha, 2009). The homeostatic proliferation of donor T cell provided by the graft and possibly also by the few residual recipient T cells is involved in the initial reconstitution of the lymphocyte compartment. Two main homeostatic cytokines are involved in this way of expansion of T cells after allograft, IL-7 and IL-15. We determined the precocious plasmatic level of these cytokines and the degree of expression of their receptor, IL-7Ralpha chain (CD127) and IL-15Rbeta chain (CD122) on the subpopulations of naive and memory T cells during the immune reconstitution post allograft. a) In 40 recipients of HSC with a myeloablative conditioning, our prospective study showed variations of IL-7 and IL-15 level during the first weeks post-graft. The plasmatic levels increased strongly to peak at day+14. Then, the concentrations return to a normal range around day+30. The increase of IL-7 and IL-15 levels observed during the first days post-graft could be due to an increase of production in response to the lymphopenia. However, at day+14 post-graft, we notice real important variations of IL-7 and IL-15 level among patients (range 3.8–30.2 and 14.3–66 pg/ml, respectively). A high level of IL-7 (≥11,9 pg/mL) at day+14 post-graft, when recipients are strongly lymphopenic, is a predictive factor of a risk of occurrence of acute GVHD (HR= 3.63 ; P= .014) compared to others factors known to favour independently this complication (reinfection to CMV, sex-mismatch). The relapse of disease is significantly associated to low level of IL-15 at day+14 (