Tissue Immune Landscape of Graft Versus Host Disease After Allogeneic Stem Cell Transplantation (TIL-GVHD)

Context : Chronic Graft versus Host Disease (cGVHD) represents the main cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (alloSCT), occurring in 30 and 60%. Translational studies showed that different alloreactive T cell subsets were involved and associated with cGVHD, and regulatory subsets were deficient. Several homeostatic abnormalities of B cell subsets were also shown, which, in the context of high BAFF level, contributed to autoreactive B cell clone emergence. In alloSCT patients, we observed (Forcade et al, Blood 2016) in the blood, a T cell subset called TFH, with B cell help capacity, similar to germinal center reaction. During cGVHD, blood TFH were highly activated, skewed toward a Th1/Th17 profile, and presented enhanced capacity to provide " help " to B cells, promoting auto-/allo-antibody production in the context of cGVHD. This was associated with increased level of CXCL13 in such patients, suggesting homing of this subset to lymphoid tissues. Liarski et al (Sci Trans Med 2014) showed that TFH were observed in inflamed tissue sample from patients with lupus, and demonstrated close interaction with B cells, mimicking germinal center structures, such as tertiary lymphoid organs. Preliminary data, on cGVHD tissue target, showed a CD4+ T cell infiltrate, of which some expressed CXCR5, ICOS, PD1 in single staining. Hypothesis : cGVHD target tissue contains tertiary lymphoid structures.