Figure 2.
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.

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.

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