Human TCM have potent effector functions, home to skin, and induce dermatitis in human engrafted mice. Human TCMhave potent effector functions, home to.

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Presentation transcript:

Human TCM have potent effector functions, home to skin, and induce dermatitis in human engrafted mice. Human TCMhave potent effector functions, home to skin, and induce dermatitis in human engrafted mice. (A,F) Both CD4+ and CD8+ TCM produced T-cell signature inflammatory cytokines. Cytokine production was assayed by CyTOF following stimulation with phorbol 12-myristate 13-acetate/ionomycin. Production of TH1/TC1 (IFN-γ), TH2/TC2 (IL-4, IL-13), TH17/TC17 (IL-17A), TH22/TC22 (IL-22) signature cytokines by TCM and TEM is shown. Figures represent the mean of 6 donors. (B,G) Total production of signature cytokines by TCM (white bars) compared with TEM from the same donors (black bars) for (B) CD4+ and (G) CD8+ T cells. (C-E,H-J) Production of IL-2, TNF-α, and IL-10 by (C-E) CD4+ and (H-J) CD8+ T cells is shown. The mean and SEM of 6 donors are shown. (K-W) Human TCM home to skin and induce an inflammatory dermatitis comparable to TEM in human engrafted mice. (K) The human engrafted mouse experimental model. (L-P) Hematoxylin and eosin evaluation of human skin grafts 3 weeks after injection of (L-M) saline, (N) TEM, (O) TCM, or (P) naive T cells. TCM homed to human skin grafts and induced T-cell–mediated inflammatory dermatitis. (P) Injection of naive T cells led to minimal inflammation. (Q-S) The inflammatory patterns induced by purified TCM included (Q) interface dermatitis, (R) spongiotic dermatitis, and (S) epidermal necrosis. Results shown are representative of those obtained with 6 different human blood cell donors. (T) T-cell migration into the skin as assessed by NanoString CD3/CD4/CD8 gene expression analysis was comparable in TCM- and TEM-injected mice. (U-V) The production of inflammatory T-cell cytokines in skin (TNF-α, IFN-γ, IL-17A, and IL-22) and cytotoxic effector molecules (PRF1, perforin; GZMA, granzyme A; GZMB, granzyme B) was comparable in TCM- and TEM-injected mice. (W) Production of inflammatory chemokines in skin was comparable in TCM- and TEM-injected mice. For panels T-W, the mean and SEM of messenger RNA copies detected by NanoString analyses from 6 different human TCM/TEM donors are shown. Scale bars, 100 μm. GVHD, graft-versus-host disease; NS, normal skin; ns, not significant. Ahmed Gehad et al. Blood Adv 2018;2:292-298 © 2018 by The American Society of Hematology