Aggregated immunoglobulin protects immune T cells from suppression: dependence on isotype, Fc portion, and macrophage FcgammaR.
Aggregated immunoglobulin protects immune T cells from suppression: dependence on isotype, Fc portion, and macrophage FcgammaR.
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聚集的免疫球蛋白可保护免疫 T 细胞免受抑制：依赖于同种型、Fc 部分和巨噬细胞 FcgammaR。
DOI：
10.1046/j.1365-3083.1998.00264.x
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发表时间：
1998
影响因子：
3.7
通讯作者：
Askenase,PW
中科院分区：
文献类型：
--
作者：
Ptak,W;Paliwal,V;Bryniarski,K;Ptak,M;Askenase,PW
我们确定了热聚集免疫球蛋白 (HA-Ig) 的调节特性，该免疫球蛋白具有免疫复合物 (IC) 的许多活性，例如通过免疫球蛋白 Fc γ 受体 (FcγR) 结合和激活细胞。 HA-Ig 保护接触敏感性 (CS) 效应 T 细胞免受抗原特异性免疫抑制，而单体 IgG 则无活性。 HA-Ig 的这种抗抑制活性是抗原非特异性的，并且取决于 Ig 来源的物种，即小鼠和大鼠 HA-Ig 对小鼠有保护作用，而其他物种则无活性。 HA-Ig 的保护活性仅限于 IgG2a 和 IgG3，对 IgG1 同种型的保护程度较小，并且位于 Fc 结构域中。从 CS 免疫靶细胞中去除吞噬细胞，或用抗 FcγR mAb 进行阻断，消除了 HA-Ig 对 CS 效应 T 细胞的抑制作用。我们认为 HA-Ig 多聚体通过 Fc 结构域以两种方式之一发挥作用：通过与巨噬细胞的 FcγR 结合产生正作用细胞因子，或通过阻断巨噬细胞上的 FcγR，与也可以与 FcγR 结合的抑制因子竞争。如果HA-Ig对T细胞的保护被普遍化，那么体内IC很可能非特异性地克服对通常在T抑制性细胞控制下的抗原反应的抑制，因此可能有助于自身免疫的发展。
We determined the regulatory properties of heat‐aggregated immunoglobulins (HA‐Ig) that possess many activities of immune complexes (IC), such as binding and activation of cells via immunoglobulin Fc γ receptors (FcγR). HA‐Ig protected contact sensitivity (CS) effector T cells from antigen‐specific immunosuppression, while monomeric IgG were inactive. This anti‐suppressive activity of HA‐Ig was antigen non‐specific, and depended on the species from which Ig was derived, i.e. mouse and rat HA‐Ig were protective in mice, and of other species were inactive. The protecting activity of HA‐Ig was confined to IgG2a and IgG3, and to a lesser degree to IgG1 isotypes, and resided in the Fc domain. Removal of phagocytic cells from the CS‐immune target cells, or blocking with anti‐FcγR mAb, abolished HA‐Ig protection of CS‐effector T cells from suppression. We suggest that HA‐Ig multimers acted via Fc domains, in one of two ways: by binding to FcγR of macrophages to produce positive‐acting cytokines, or by blocking FcγR on macrophages, to compete with suppressive factors that can also bind to FcγR. If HA‐Ig protection of T cells is generalized, it is likely that ICin vivomay non‐specifically overcome suppression of responses to antigen that normally are under the control of T suppressive cells, and thus may contribute to the development of autoimmunity.