Losana Giuliana, Bovolenta Chiara, Rigamonti Laura, Borghi Igor, Altare Frederic, Jouanguy Emmanuelle, Forni Guido, Casanova Jean-Laurent, Sherry Barbara, Mengozzi Manuela, Trinchieri Giorgio, Poli Guido, Gerosa Franca, Novelli Francesco
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
J Leukoc Biol. 2002 Oct;72(4):735-42.
Interleukin (IL)-12, especially in the presence of neutralizing anti-IL-4 monoclonal antibodies, primed CD45RO(-) T clones for high CCL3/macrophage-inflammatory protein-1alpha (MIP-1alpha) and CCL4/MIP-1beta levels. In CD4(+) and CD8(+) clones from two patients deficient for IL-12Rbeta1 (IL-12Rbeta1(-/-)), production of CCL3/MIP-1alpha and CCL4/MIP-1beta was defective. CD4(+) clones from two patients deficient for interferon-gamma (IFN-gamma) R1 (IFN-gammaR1(-/-)) produced somewhat decreased CCL4/MIP-1beta levels. IL-12 failed to prime CD4(+) or CD8(+) healthy clones for high CCL5/regulated on activation, normal T expressed and secreted (RANTES) production, although its secretion was impaired in CD4(+) clones from IL-12Rbeta1(-/-) and IFN-gammaR1(-/-) patients. CCR5 surface expression was up-regulated in resting peripheral blood mononuclear cells and CD4(+) clones from both kinds of patients, rendering them more susceptible to CCR5-dependent (R5) HIV-1 infection. Neutralization of IFN-gamma increased CCR5 expression and decreased CC-chemokine secretion by CD4(+) clones from healthy and IL-12Rbeta1(-/-) individuals, suggesting an IFN-gamma-dependent control of CCR5 expression. These data provide the first documented analysis of chemokine secretion and chemokine receptor expression on T cells from IL-12 and IFN-gamma receptor-deficient patients and dissect the role of IL-12 and IFN-gamma on inducing inflammatory chemokine secretion and down-regulating CCR5 expression in human T cells.
白细胞介素（IL）-12，尤其是在存在中和性抗IL-4单克隆抗体的情况下，可使CD45RO（-）T细胞克隆预先准备好产生高水平的CCL3/巨噬细胞炎性蛋白-1α（MIP-1α）和CCL4/MIP-1β。在两名IL-12Rβ1缺陷（IL-12Rβ1（-/-））患者的CD4（+）和CD8（+）克隆中，CCL3/MIP-1α和CCL4/MIP-1β的产生存在缺陷。两名干扰素-γ（IFN-γ）R1缺陷（IFN-γR1（-/-））患者的CD4（+）克隆产生的CCL4/MIP-1β水平有所降低。IL-12未能使健康的CD4（+）或CD8（+）克隆预先准备好产生高水平的CCL5/活化调节正常T细胞表达和分泌因子（RANTES），尽管在IL-12Rβ1（-/-）和IFN-γR1（-/-）患者的CD4（+）克隆中其分泌受损。在静息外周血单核细胞以及两类患者的CD4（+）克隆中，CCR5表面表达上调，使它们更容易受到CCR5依赖性（R5）HIV-1感染。中和IFN-γ可增加健康个体和IL-12Rβ1（-/-）个体的CD4（+）克隆的CCR5表达并降低CC趋化因子分泌，提示存在IFN-γ依赖性的CCR5表达调控。这些数据首次对IL-12和IFN-γ受体缺陷患者T细胞上的趋化因子分泌和趋化因子受体表达进行了记录分析，并剖析了IL-12和IFN-γ在诱导人T细胞炎性趋化因子分泌和下调CCR5表达中的作用。
Proc Natl Acad Sci U S A. 2002-4-30
J Leukoc Biol. 2004-9
Cytokine Growth Factor Rev. 2004-10
Proc Natl Acad Sci U S A. 2004-4-27
Zotero 插件