Krifuks O, Bergelson L D, Schlesinger M
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Cell Immunol. 1998 Jul 10;187(1):45-51. doi: 10.1006/cimm.1998.1311.
The involvement of protein kinases and phosphatases in the down-modulation of expression of CD4 molecules on peripheral blood lymphocytes (PBL) by gangliosides was studied. Exposure of PBL either to genistein or to H7 practically abolished the down-modulation of CD4 induced by GM1 and diminished their susceptibility to CD4+ down-modulation by exposure to GD1a. Staurosporine had no effect on the down-modulation of CD4 by either GM1 or GD1a. Orthovanadate treatment drastically inhibited the down-regulation of CD4 induced by GM1 but had no effect on down-modulation of CD4 induced by GD1a. Exposure to monoclonal antibodies (mAbs) against CD45 and CD45RA but not against CD45RO abrogated the down-modulation of CD4 by GM1. The down-modulation of CD4 elicited by GD1a, GD1b, or GT1b was not inhibited by anti-CD45RA and anti-CD45RO mAbs. MAbs against CD3, CD2, or HLA-DR had no effect on the GM1-induced down-modulation of CD4. In view of the differences obtained between GM1 and GD1a it was of interest to check whether these gangliosides competed for cellular binding sites. When PBL were first treated with anti-CD45RA and GM1 or with orthovanadate and GM1, which had a negligible effect on CD4 expression, and subsequently treated with GD1a the expression of CD4 was down-modulated. This demonstrated that GD1a binds to sites on the cell membrane to which GM1 does not bind. The present study indicates that the capacity of GM1 to down-modulate CD4 depended on the CD45 and particularly CD45RA molecules, while other gangliosides may utilize different cell surface structures to down-modulate the expression of CD4.
研究了蛋白激酶和磷酸酶在神经节苷脂对外周血淋巴细胞（PBL）上CD4分子表达的下调作用中的参与情况。PBL暴露于染料木黄酮或H7实际上消除了GM1诱导的CD4下调，并降低了它们因暴露于GD1a而对CD4 +下调的敏感性。星形孢菌素对GM1或GD1a诱导的CD4下调均无影响。原钒酸盐处理强烈抑制了GM1诱导的CD4下调，但对GD1a诱导的CD4下调无影响。暴露于抗CD45和CD45RA而非抗CD45RO的单克隆抗体（mAb）可消除GM1对CD4的下调。GD1a、GD1b或GT1b引起的CD4下调不受抗CD45RA和抗CD45RO mAb的抑制。抗CD3、CD2或HLA - DR的mAb对GM1诱导的CD4下调无影响。鉴于GM1和GD1a之间存在差异，研究它们是否竞争细胞结合位点很有意义。当PBL先用抗CD45RA和GM1或原钒酸盐和GM1处理（这对CD4表达影响可忽略不计），随后再用GD1a处理时，CD4的表达被下调。这表明GD1a结合到GM1不结合的细胞膜位点上。本研究表明，GM1下调CD4的能力取决于CD45，特别是CD45RA分子，而其他神经节苷脂可能利用不同的细胞表面结构来下调CD4的表达。
