Amin Parth B, Diebel Lawrence N, Liberati David M
Department of Surgery, Wayne State University, 4201 St. Antoine St., Suite 6C, University Health Center, Detroit, MI 48201, USA.
Am J Surg. 2007 Jul;194(1):128-33. doi: 10.1016/j.amjsurg.2006.11.026.
Secretory immunoglobulin A (sIgA) is the principle immune defense against bacteria and other pathogens in the gut and other mucosal surfaces. sIgA is produced locally by plasma cells and transported (transcytosis) across epithelial cells into luminal secretions. sIgA production and transcytosis are governed by multiple signals, which may be affected by T cells. The purpose of this study was to elucidate the role of the Th1-type cytokine, interferon gamma (IFN-gamma), and the Th2-type cytokine interleukin-4 (IL-4) on IgA transcytosis across intestinal epithelial cells in vitro.
HT-29 cell monolayers were established in a 2-chamber cell culture system. Cell monolayers were exposed to either IFN-gamma, IL-4, or both on the apical or basal side of the culture system systems for 48 hours. Dimeric IgA then was added to the basolateral chamber and transcytosis into the apical chamber was quantified by enzyme-linked immunosorbent assay at timed intervals. IgA transcytosis across HT-29 cells without prior addition of either cytokine served as a control.
Poly Ig-receptor up-regulation was shown by both IFN and IL-4. A combination of these 2 cytokines caused the greatest increase in receptor expression. A total of 3.7% of HT-29 cells expressed the polymeric Ig receptor in the control group. This increased to 23.7% in IL-4-treated cells, 66.3% in IFN-gamma-treated cells, and 71.5% of cells treated with both cytokines. These findings re-show previously published findings. The effects of IFN-gamma added to the basal chamber of HT-29 cell cultures shows a 7- to 10-fold increase in sIgA transcytosis at the 1-, 3-, and 12-hour time intervals. The effect of the addition of IL-4 to the basal chamber was similar to the results noted with IFN-gamma alone. The greatest IgA transcytosis was noted when IFN-gamma and IL-4 both were added to the basal chamber. However, these same results did not occur with cytokine exposure to the apical side of cell monolayers.
IFN-gamma and IL-4 increased IgA transport across HT-29 cells in a polar fashion. An increased effect on IgA transport was noted with the combination of IFN-gamma and IL-4. Delivery of T-cell cytokines to mucosal surfaces may support local antibody defense of mucosal surfaces and prevent infection.
分泌型免疫球蛋白A（sIgA）是肠道及其他黏膜表面抵御细菌和其他病原体的主要免疫防线。sIgA由浆细胞在局部产生，并通过上皮细胞转运（转胞吞作用）至管腔分泌物中。sIgA的产生和转胞吞作用受多种信号调控，这些信号可能受T细胞影响。本研究的目的是阐明Th1型细胞因子干扰素γ（IFN-γ）和Th2型细胞因子白细胞介素-4（IL-4）在体外对IgA跨肠上皮细胞转胞吞作用的影响。
在双室细胞培养系统中建立HT-29细胞单层。将细胞单层在培养系统的顶端或基底侧暴露于IFN-γ、IL-4或两者中48小时。然后将二聚体IgA添加至基底室，并在不同时间间隔通过酶联免疫吸附测定法定量其向顶端室的转胞吞作用。未预先添加任何一种细胞因子的情况下IgA跨HT-29细胞的转胞吞作用作为对照。
IFN和IL-4均显示出多聚免疫球蛋白受体上调。这两种细胞因子联合使用导致受体表达增加最为显著。对照组中共有3.7%的HT-29细胞表达多聚免疫球蛋白受体。在IL-4处理的细胞中这一比例增至23.7%，在IFN-γ处理的细胞中为66.3%，在两种细胞因子都处理的细胞中为71.5%。这些发现再次证实了先前发表的结果。添加至HT-29细胞培养基底室的IFN-γ在1小时、3小时和12小时间隔时使sIgA转胞吞作用增加7至10倍。添加至基底室的IL-4的作用与单独使用IFN-γ时的结果相似。当IFN-γ和IL-4都添加至基底室时观察到最大的IgA转胞吞作用。然而，当细胞单层顶端暴露于细胞因子时未出现相同结果。
IFN-γ和IL-4以极性方式增加IgA跨HT-29细胞的转运。IFN-γ和IL-4联合使用对IgA转运具有增强作用。将T细胞细胞因子递送至黏膜表面可能支持黏膜表面的局部抗体防御并预防感染。
