LOCAL ENTRAPMENT OF INTERFERON-GAMMA IN THE RECOVERY FROM SHIGELLA-DYSENTERIAE TYPE-1 INFECTION

In healthy controls (n = 8) living in shigella endemic areas, accumula tion of interferon gamma (IFN gamma) in the epithelial lining was seen in the rectal tissues. At the single cell level, however, few or no I FN gamma protein producing cells or mRNA expressing cells were detecte d at that site indicating the involvement of the whole large intestine in the production of IFN gamma in controls. Persistent numbers of IFN gamma producing cells were detected in tbe rectum of patients with Sh igella dysenteriae type 1 infection (n = 8) throughout the course of d isease with a tendency to increase in the convalescent stage. A signif icantly increased extra cellular deposition of secreted IFN gamma in t issue was seen in convalescence when compared with the acute stage (p< 0.05). In addition, enzyme immunoassay showed increased stool concentr ation of IFN gamma in patients at the convalescent stage as well as in healthy controls. In situ hybridisation confirmed the results by show ing increased frequency of IFN gamma mRNA containing cells at the late stage of the disease (p<0.05). Extensive message for IFN gamma was ev ident in cells in the lamina propria with no detectable transcripts in the surface epithelium. A colocalisation of IFN gamma with the IFN ga mma receptor expression, predominantly found in the epithelial lining was detected by immunohistochemistry. Semiquantitative evaluation by c omputerised image analysis showed a gradual increased expression of IF N gamma and its corresponding receptor in the convalescent stage of sh igellosis. This suggested progressive entrapment and binding of IFN ga mma to its specific receptor at the local site. The enhanced surface e xpression of IFN gamma receptor evident at the convalescent stage of s higellosis was comparable to the constitutive level of expression in t he healthy subjects. Thus, immunity to shigellosis correlated to up-re gulation of IFN gamma production and expression of IFN gamma receptor.