TNF enhances CD4+ T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease by IL-12-independent mechanisms

Geri Brown, Edward L. Lee, Dwain L Thiele

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23 Citations (Scopus)

Abstract

Inhibition of TNF/TNFR2 interactions ameliorates intestinal graft-vs-host disease (GVHD) and Th1 cytokine responses induced by transfer of B6 CD4+ spleen cells into irradiated MHC class II disparate B6.C-H-2bm12 (bm12) × B6 F1 recipients. The present studies examined whether these effects of TNF are IL-12 dependent. T cell proliferative responses of B6.129S1-IL-12rb2tm1Jm (B6.IL-12R-/-) responder spleen cells were found to be comparable to those of control B6 spleen cells. TNF inhibition reduced T cell proliferation and IFN-γ production in supernatants of MLC using either B6.IL-12R-/- or control B6 responder cells. GVHD induced wasting disease in recipients of B6.IL-12R-/- CD4+ spleen cells that received a TNF inhibitor-encoding adenovirus (5.4 ± 6.5% weight loss (n = 7)) was significantly reduced compared with levels of weight loss observed in recipients that had received a control adenovirus (25.7 ± 12.2% weight loss (n = 11), p = 0.001). Furthermore, TNF inhibition was associated with a reduction in colonic GVHD scores (p = 0.039) and in the percentage of the splenic CD4+ T cells that expressed IFN-γ (16 vs 6%). These findings indicate that TNF promotes CD4+ T cell alloproliferation, IFN-γ responses, and intestinal GVHD by IL-12-independent mechanisms.

Original languageEnglish (US)
Pages (from-to)5082-5088
Number of pages7
JournalJournal of Immunology
Volume170
Issue number10
StatePublished - May 15 2003

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Graft vs Host Disease
Interleukin-12
T-Lymphocytes
Spleen
Weight Loss
Adenoviridae
Receptors, Tumor Necrosis Factor, Type II
Wasting Syndrome
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "TNF enhances CD4+ T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease by IL-12-independent mechanisms",
abstract = "Inhibition of TNF/TNFR2 interactions ameliorates intestinal graft-vs-host disease (GVHD) and Th1 cytokine responses induced by transfer of B6 CD4+ spleen cells into irradiated MHC class II disparate B6.C-H-2bm12 (bm12) × B6 F1 recipients. The present studies examined whether these effects of TNF are IL-12 dependent. T cell proliferative responses of B6.129S1-IL-12rb2tm1Jm (B6.IL-12R-/-) responder spleen cells were found to be comparable to those of control B6 spleen cells. TNF inhibition reduced T cell proliferation and IFN-γ production in supernatants of MLC using either B6.IL-12R-/- or control B6 responder cells. GVHD induced wasting disease in recipients of B6.IL-12R-/- CD4+ spleen cells that received a TNF inhibitor-encoding adenovirus (5.4 ± 6.5{\%} weight loss (n = 7)) was significantly reduced compared with levels of weight loss observed in recipients that had received a control adenovirus (25.7 ± 12.2{\%} weight loss (n = 11), p = 0.001). Furthermore, TNF inhibition was associated with a reduction in colonic GVHD scores (p = 0.039) and in the percentage of the splenic CD4+ T cells that expressed IFN-γ (16 vs 6{\%}). These findings indicate that TNF promotes CD4+ T cell alloproliferation, IFN-γ responses, and intestinal GVHD by IL-12-independent mechanisms.",
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T1 - TNF enhances CD4+ T cell alloproliferation, IFN-γ responses, and intestinal graft-versus-host disease by IL-12-independent mechanisms

AU - Brown, Geri

AU - Lee, Edward L.

AU - Thiele, Dwain L

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N2 - Inhibition of TNF/TNFR2 interactions ameliorates intestinal graft-vs-host disease (GVHD) and Th1 cytokine responses induced by transfer of B6 CD4+ spleen cells into irradiated MHC class II disparate B6.C-H-2bm12 (bm12) × B6 F1 recipients. The present studies examined whether these effects of TNF are IL-12 dependent. T cell proliferative responses of B6.129S1-IL-12rb2tm1Jm (B6.IL-12R-/-) responder spleen cells were found to be comparable to those of control B6 spleen cells. TNF inhibition reduced T cell proliferation and IFN-γ production in supernatants of MLC using either B6.IL-12R-/- or control B6 responder cells. GVHD induced wasting disease in recipients of B6.IL-12R-/- CD4+ spleen cells that received a TNF inhibitor-encoding adenovirus (5.4 ± 6.5% weight loss (n = 7)) was significantly reduced compared with levels of weight loss observed in recipients that had received a control adenovirus (25.7 ± 12.2% weight loss (n = 11), p = 0.001). Furthermore, TNF inhibition was associated with a reduction in colonic GVHD scores (p = 0.039) and in the percentage of the splenic CD4+ T cells that expressed IFN-γ (16 vs 6%). These findings indicate that TNF promotes CD4+ T cell alloproliferation, IFN-γ responses, and intestinal GVHD by IL-12-independent mechanisms.

AB - Inhibition of TNF/TNFR2 interactions ameliorates intestinal graft-vs-host disease (GVHD) and Th1 cytokine responses induced by transfer of B6 CD4+ spleen cells into irradiated MHC class II disparate B6.C-H-2bm12 (bm12) × B6 F1 recipients. The present studies examined whether these effects of TNF are IL-12 dependent. T cell proliferative responses of B6.129S1-IL-12rb2tm1Jm (B6.IL-12R-/-) responder spleen cells were found to be comparable to those of control B6 spleen cells. TNF inhibition reduced T cell proliferation and IFN-γ production in supernatants of MLC using either B6.IL-12R-/- or control B6 responder cells. GVHD induced wasting disease in recipients of B6.IL-12R-/- CD4+ spleen cells that received a TNF inhibitor-encoding adenovirus (5.4 ± 6.5% weight loss (n = 7)) was significantly reduced compared with levels of weight loss observed in recipients that had received a control adenovirus (25.7 ± 12.2% weight loss (n = 11), p = 0.001). Furthermore, TNF inhibition was associated with a reduction in colonic GVHD scores (p = 0.039) and in the percentage of the splenic CD4+ T cells that expressed IFN-γ (16 vs 6%). These findings indicate that TNF promotes CD4+ T cell alloproliferation, IFN-γ responses, and intestinal GVHD by IL-12-independent mechanisms.

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