MORPHOLOGIC AND ANTIGENIC CHARACTERIZATION OF INTERFERON GAMMA-MEDIATED PERSISTENT CHLAMYDIA-TRACHOMATIS INFECTION INVITRO

An in vitro cell culture system was used to study the effect of interf eron gamma (IFN-gamma) on Chlamydia trachomatis growth and differentia tion. The effect of IFN-gamma on chlamydiae was dose-dependent. IFN-ga mma at 2 ng/ml completely inhibited chlamydial growth and differentiat ion; however, persistent infection was established when chlamydiae wer e cultured with IFN-gamma at 0.2 ng/ml. Persistent infection was chara cterized by the development of noninfectious atypical chlamydial forms from which infectious progeny could be recovered only when IFN-gamma was removed from the culture system. Analysis of persistently infected cells by immunofluorescent microscopy and immunoblotting with specifi c antibodies revealed that the atypical chlamydial forms had near-norm al levels of the 60-kDa heat shock protein, an immunopathologic antige n, and a paucity of the major outer membrane protein, a protective ant igen. Furthermore, steady-state levels of other outer membrane constit uents, such as the 60-kDa cysteine-rich outer membrane protein and lip opolysaccharide, were greatly reduced. If IFN-gamma causes similar eve nts to occur in vivo, then persistently infected cells could augment t he pathogenesis of the chronic inflammatory sequelae that follow chlam ydial infection by serving as depots of antigen capable of stimulating a sustained inflammatory response.