TY - JOUR
T1 - TNF-TNFR2 interactions are critical for the development of intestinal graft-versus-host disease in MHC class II-disparate (C57BL/6J→C57BL/6J × bm12)F1 mice
AU - Brown, Geri
AU - Lee, Ed
AU - Thiele, Dwain L
PY - 2002/3/15
Y1 - 2002/3/15
N2 - TNF-TNFR2 interactions promote MHC class II-stimulated alloresponses while TNF-TNFR1 interactions promote MHC class I-stimulated alloresponses. The present studies were designed to evaluate whether TNF-TNFR2 interactions were involved in the in vivo generation of CD4+ T cell-mediated intestinal graft-versus-host disease (GVHD) in the (C57BL/6J (hereafter called B6)→B6 × B6.C-H-2bm12 (bm12))F1 GVHD model. Briefly, 5 × 106 splenic CD4+ T lymphocytes from B6.TNFR2-/- or control B6 mice were transferred with 1-2 × 106 T cell-depleted B6 bone marrow cells (BMC) to irradiated MHC class II-disparate (bm12 × B6)F1 mice. Weight loss, intestinal inflammation, and the surface expression of CD45RB (memory marker) on intestinal and splenic lymphocytes were assessed. IL-2 and IFN-α mRNA levels in intestinal lymphocytes were assessed by nuclease protection assays. A significant reduction in weight loss and intestinal inflammation was observed in recipients of the TNFR2-/-CD4+ SpC. Similarly, a significant decrease was noted in T cell numbers and in CD45RBlow (activated/memory) expression on intestinal but not CD4+ T cells in recipients of TNFR2-/-CD4+ spleen cells. IL-2 and IFN-α mRNA levels were reduced in the intestine in the recipients of TNFR2-/- splenic CD4+ T cells. These results indicate that TNF-TNFR2 interactions are important for the development of intestinal inflammation and activation/differentiation of Th1 cytokine responses by intestinal lymphocytes in MHC class II-disparate GVHD while playing an insignificant role in donor T cell activation in the spleen.
AB - TNF-TNFR2 interactions promote MHC class II-stimulated alloresponses while TNF-TNFR1 interactions promote MHC class I-stimulated alloresponses. The present studies were designed to evaluate whether TNF-TNFR2 interactions were involved in the in vivo generation of CD4+ T cell-mediated intestinal graft-versus-host disease (GVHD) in the (C57BL/6J (hereafter called B6)→B6 × B6.C-H-2bm12 (bm12))F1 GVHD model. Briefly, 5 × 106 splenic CD4+ T lymphocytes from B6.TNFR2-/- or control B6 mice were transferred with 1-2 × 106 T cell-depleted B6 bone marrow cells (BMC) to irradiated MHC class II-disparate (bm12 × B6)F1 mice. Weight loss, intestinal inflammation, and the surface expression of CD45RB (memory marker) on intestinal and splenic lymphocytes were assessed. IL-2 and IFN-α mRNA levels in intestinal lymphocytes were assessed by nuclease protection assays. A significant reduction in weight loss and intestinal inflammation was observed in recipients of the TNFR2-/-CD4+ SpC. Similarly, a significant decrease was noted in T cell numbers and in CD45RBlow (activated/memory) expression on intestinal but not CD4+ T cells in recipients of TNFR2-/-CD4+ spleen cells. IL-2 and IFN-α mRNA levels were reduced in the intestine in the recipients of TNFR2-/- splenic CD4+ T cells. These results indicate that TNF-TNFR2 interactions are important for the development of intestinal inflammation and activation/differentiation of Th1 cytokine responses by intestinal lymphocytes in MHC class II-disparate GVHD while playing an insignificant role in donor T cell activation in the spleen.
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U2 - 10.4049/jimmunol.168.6.3065
DO - 10.4049/jimmunol.168.6.3065
M3 - Article
C2 - 11884480
AN - SCOPUS:0037087341
SN - 0022-1767
VL - 168
SP - 3065
EP - 3071
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -