Immunomodulatory effects of interferon-γ on autoreactive nephritogenic T-cell clones
Authors: Catherine M. Meyers, Youkang Zhang
Journal: Kidney International (1999)

Immunomodulatory effects of interferon-γ on autoreactive nephritogenic T-cell clones.BackgroundWe examined the immunomodulatory effects of interferon-γ (IFN-γ) on renal-derived CD4+ α/β+ T cells, called mouse renal (MR) cells, isolated from animals with murine chronic graft-versus-host disease, a model of autoimmune glomerulonephritis. MR T cells express a Th2 cytokine profile, although IFN-γ expression is also detected in a subset of clones that adoptively transfers renal disease to naive recipients. In view of disparate patterns of IFN-γ expression, we evaluated the effects of exogenous IFN-γ on nephritogenic (MR1.3) and nonnephritogenic (MR1.6) clonal activity.MethodsThese studies examined IFN-γ–mediated effects on clonal proliferation, cytokine production, nephritogenic potential, and IFN-γ receptor expression.ResultsIFN-γ mediated dose-dependent inhibition of MR1.3 and MR1.6 proliferation. This cytostatic effect was not mediated by inhibiting cytokine genes, as expression of interleukin (IL)-4, IL-10, IL-13, and IFN-γ after IFN-γ treatment was not markedly altered in either clone, although baseline IL-13 expression was enhanced in MR1.6. IFN-γ markedly altered the functional phenotype of MR1.6, as pretreated recipients developed severe mononuclear cell infiltrates and tubular damage following adoptive transfer of MR1.6. Neutralizing anti–IFN-γ antibodies did not inhibit MR1.3 nephritogenicity, but did block MR1.6-induced disease in IFN-γ–treated mice. Although both clones constitutively expressed the IFN-γ receptor β chain, IFN-γ exposure decreased its expression in MR1.3 cells, but did not markedly change its expression in MR1.6 cells.ConclusionThese studies describe an unusual permissive role for IFN-γ in modulating nephritogenic Th2 activity in vivo, which facilitates the initiation of cell-mediated autoimmune renal injury. Apparent differential effects of IFN-γ on distinct T-cell clones may be mediated in part by alterations in cytokine receptor expression. Immunomodulatory effects of interferon-γ on autoreactive nephritogenic T-cell clones. We examined the immunomodulatory effects of interferon-γ (IFN-γ) on renal-derived CD4+ α/β+ T cells, called mouse renal (MR) cells, isolated from animals with murine chronic graft-versus-host disease, a model of autoimmune glomerulonephritis. MR T cells express a Th2 cytokine profile, although IFN-γ expression is also detected in a subset of clones that adoptively transfers renal disease to naive recipients. In view of disparate patterns of IFN-γ expression, we evaluated the effects of exogenous IFN-γ on nephritogenic (MR1.3) and nonnephritogenic (MR1.6) clonal activity. These studies examined IFN-γ–mediated effects on clonal proliferation, cytokine production, nephritogenic potential, and IFN-γ receptor expression. IFN-γ mediated dose-dependent inhibition of MR1.3 and MR1.6 proliferation. This cytostatic effect was not mediated by inhibiting cytokine genes, as expression of interleukin (IL)-4, IL-10, IL-13, and IFN-γ after IFN-γ treatment was not markedly altered in either clone, although baseline IL-13 expression was enhanced in MR1.6. IFN-γ markedly altered the functional phenotype of MR1.6, as pretreated recipients developed severe mononuclear cell infiltrates and tubular damage following adoptive transfer of MR1.6. Neutralizing anti–IFN-γ antibodies did not inhibit MR1.3 nephritogenicity, but did block MR1.6-induced disease in IFN-γ–treated mice. Although both clones constitutively expressed the IFN-γ receptor β chain, IFN-γ exposure decreased its expression in MR1.3 cells, but did not markedly change its expression in MR1.6 cells. These studies describe an unusual permissive role for IFN-γ in modulating nephritogenic Th2 activity in vivo, which facilitates the initiation of cell-mediated autoimmune renal injury. Apparent differential effects of IFN-γ on distinct T-cell clones may be mediated in part by alterations in cytokine receptor expression.