T-HELPER TYPE-1 (TH1) TH2 PROFILES OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS (PBMC) - RESPONSES TO ANTIGENS OF CHLAMYDIA-TRACHOMATIS IN SUBJECTS WITH SEVERE TRACHOMATOUS SCARRING/

Increased stimulation of Th2 cytokines may contribute to the developme nt of persistent ocular chlamydial infection, resulting in the blindin g pathological changes of trachoma. Proliferation and cytokine product ion profiles of PBMC in response to stimulation with antigens of Chlam ydia trachomatis were compared in 30 patients with severe conjunctival scarring due to trachoma and in 30 age-, sex- and location-matched co ntrols. Interferon-gamma (IFN-gamma) and IL-4 were detected at the sin gle-cell level by ELISPOT assay. Transcription of the genes encoding I FN-gamma, IL-4 and IL-10 was detected in mRNA isolated from parallel c ultures of PBMC using reverse transcriptase-polymerase chain reaction (RT-PCR). incubation with the chlamydial heat shock protein (hsp)60 re sulted in increased numbers of IL-4-producing cells in PBMC isolated f rom patients with scarring disease and increased secretion of IFN-gamm a from PBMC of control subjects. Incubation with the chlamydial major outer membrane protein (MOMP) increased the number of IFN-gamma-produc ing cells in the control group only. Messenger RNA encoding IL-4 was o nly detected in PBMC of patients with scarring disease after in vitro stimulation with chlamydial antigens, bur IFN-gamma mRNA and IL-10 mRN A were also more frequently detected in this group. Thirty-eight subje cts were HLA-DRB1 and -DQB1 typed. Associations were observed between certain HLA class II alleles and cellular immune responses to chlamydi al antigens. No HLA associations were found with clinical status, and overall we found no evidence of strong associations and the type of im mune response. These data are consistent with a role for Th2 cells and cytokines in the pathogenesis of trachomatous scarring.