Figure 1.
Donor-derived IL-17+and RORγt+Th17 cells develop early after allo-SCT in an IL-6-dependent manner. (A-G) CD4+YFP+ development was assessed in spleen, mesenteric LN (mLN), peripheral LN (pLN) and liver from lethally irradiated allogeneic (B6.IL-17CreRosa26eYFP → B6D2F1) or (B) syngeneic (B6.IL-17CreRosa26eYFP → B6) mice transplanted with G-CSF mobilized grafts. (A) Time course analysis of CD4+YFP+ frequencies and absolute numbers within the CD4+ T-cell compartment d3, d7, d14, and d21 posttransplant (mean ± SEM, n = 4-21 mice per group pooled from 2-4 independent experiments). (B) CD4+YFP+ frequencies and absolute numbers 7 days after syngeneic or allogeneic SCT (mean ± SEM, n = 7-9 mice per group pooled from 2 independent experiments, **P < .01, ***P < .001). (C) CD4+YFP+ frequencies and absolute numbers 7 days after allogeneic SCT in the presence of either IL-6R blocking mAbs or control IgG (mean ± SEM, n = 10 mice per group pooled from 2 independent experiments, ***P < .001). (D) IL-17A expression in naive and donor CD4+ T cells d7 and d21 after transplant in (D-E) spleen and (E) liver (mean ± SEM, n = 10-15 mice per group pooled from 2-3 independent experiments, **P < .01, ***P < .001). (F) YFP+ and YFP– CD4+ T cells isolated from spleen, LNs, and liver by FACS on d7 and d21 followed by qPCR (mean ± SEM, n = 3-4 independent experiments each composed of 10 pooled mice per group, *P < .05). (G) RORγt and Tbet expression by CD4+ T-cell populations isolated from spleen, mLNs, and liver d7 posttransplant.