Figure 7
Figure 7. Socs3−/ΔLck T cells exacerbate scleroderma in an IFNγ- and TGFβ-dependent manner. WT or SOCS3−/ΔLck donors were treated with G-CSF, and unfractionated splenocytes containing 3.5 million T cells or T cell–depleted grafts were transplanted into lethally irradiated LP/J recipient mice. (A) Representative images of hematoxylin and eosin–stained skin taken day 14 after transplantation (magnification ×250). (B) Transplant recipients received T cell replete or T cell–depleted grafts from G-CSF–treated WT or SOCS3−/ΔLck donors, and skin histopathology was assessed at day 14 after transplantation as described in “Histology” (n = 12 animals per GVHD group, n = 3 animals per TCD group from 2 replicate experiments). *P < .001, WT versus SOCS3−/ΔLck. (C) Irradiated LP/J transplant recipients of SOCS3−/ΔLck grafts received isotype control mAb or anti–IL-17, anti–IL-10R, anti-IFNγ, or anti-TGFβ mAb thrice/week from day 0 onward. Skin histopathology was assessed at days 14 to 19. Data were pooled from 3 similar experiments (n = 4-17 animals per GVHD group, n = 6 animals per TCD group). Top and bottom dotted lines delineate pathology scores for control GVHD and non-GVHD groups, respectively. (D) Representative images of hematoxylin and eosin–stained skin taken day 14 after transplantation in animals receiving control IgG or anti-IFNγ or anti-TGFβ (magnification ×250). *P < .01, control versus blocking antibody.

Socs3−/ΔLck T cells exacerbate scleroderma in an IFNγ- and TGFβ-dependent manner. WT or SOCS3−/ΔLck donors were treated with G-CSF, and unfractionated splenocytes containing 3.5 million T cells or T cell–depleted grafts were transplanted into lethally irradiated LP/J recipient mice. (A) Representative images of hematoxylin and eosin–stained skin taken day 14 after transplantation (magnification ×250). (B) Transplant recipients received T cell replete or T cell–depleted grafts from G-CSF–treated WT or SOCS3−/ΔLck donors, and skin histopathology was assessed at day 14 after transplantation as described in “Histology” (n = 12 animals per GVHD group, n = 3 animals per TCD group from 2 replicate experiments). *P < .001, WT versus SOCS3−/ΔLck. (C) Irradiated LP/J transplant recipients of SOCS3−/ΔLck grafts received isotype control mAb or anti–IL-17, anti–IL-10R, anti-IFNγ, or anti-TGFβ mAb thrice/week from day 0 onward. Skin histopathology was assessed at days 14 to 19. Data were pooled from 3 similar experiments (n = 4-17 animals per GVHD group, n = 6 animals per TCD group). Top and bottom dotted lines delineate pathology scores for control GVHD and non-GVHD groups, respectively. (D) Representative images of hematoxylin and eosin–stained skin taken day 14 after transplantation in animals receiving control IgG or anti-IFNγ or anti-TGFβ (magnification ×250). *P < .01, control versus blocking antibody.

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