MacMillan Heather F, Lee Tim, Issekutz Andrew C
Department of Pathology, Dalhousie University, Nova Scotia, Canada.
Clin Immunol. 2009 Aug;132(2):222-33. doi: 10.1016/j.clim.2009.04.002. Epub 2009 May 17.
Commercial intravenous immunoglobulin G (IVIG) at high doses has therapeutic benefit in autoimmune and inflammatory diseases. It has been shown to inhibit T-cell function but the mechanisms are unclear. Inhibition could result from IVIG processing, donor pooling or intrinsic downregulatory activity of IgG. To address these points, we compared the effects on T-cell activation of IVIG, Fab(2) fragment and IgG isolated from single-donor plasma. We also investigated the role of accessory cells in the IVIG effects using highly purified T cells stimulated through CD3 and CD28 engagement. T-cell proliferation was evaluated by Oregon Green 488 dye dilution and (3)H-thymidine incorporation. IVIG, Fab(2) fragment of IVIG and autologous, single-donor IgG significantly inhibited T-cell proliferation (35-50%), even in the absence of accessory cells. Depletion of IgG from plasma used for culture significantly increased (by 50%) the T-cell proliferation. The addition of physiological concentrations of single-donor, autologous IgG or IVIG to IgG-depleted plasma reduced T-cell proliferation to levels observed in normal plasma. Therefore, donor pooling in IVIG and accessory cells are not required for inhibition of T-cell proliferation by IVIG and the Fab(2) region is sufficient to mediate this inhibition. Suppression of T-cell activation by IVIG likely reflects a physiologic, endogenous mechanism of IgG-mediated regulation of T-cell activation.
高剂量的商业静脉注射免疫球蛋白G（IVIG）在自身免疫性疾病和炎症性疾病中具有治疗作用。已证明其可抑制T细胞功能，但机制尚不清楚。抑制作用可能源于IVIG的加工、供体混合或IgG固有的下调活性。为解决这些问题，我们比较了IVIG、Fab(2)片段和从单供体血浆中分离的IgG对T细胞活化的影响。我们还使用通过CD3和CD28结合刺激的高度纯化T细胞研究了辅助细胞在IVIG作用中的作用。通过俄勒冈绿488染料稀释和³H-胸腺嘧啶掺入评估T细胞增殖。IVIG、IVIG的Fab(2)片段以及自体单供体IgG均显著抑制T细胞增殖（35%-50%），即使在没有辅助细胞的情况下也是如此。用于培养的血浆中IgG的消耗显著增加（50%）T细胞增殖。向IgG耗尽的血浆中添加生理浓度的单供体、自体IgG或IVIG可将T细胞增殖降低至正常血浆中观察到的水平。因此，IVIG中的供体混合和辅助细胞并非IVIG抑制T细胞增殖所必需，且Fab(2)区域足以介导这种抑制作用。IVIG对T细胞活化的抑制可能反映了IgG介导的T细胞活化调节的一种生理、内源性机制。
