T-cell cytokines affect mucosal immunoglobulin A transport

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.