Year: 2002
Type: article
Study design: Observational Study
Abstract: The purpose of this study was to elucidate the role of chlamydial 60 kDa heat shock protein (CHSP60) induced cell-mediated immune (CMI) response in women with tubal factor infertility (TFI).Chlamydia trachomatis is the major cause of sexually transmitted bacterial infections (STIs) worlwide.Most chlamydial infections are asymptomatic or show mild symptoms and are thus often left untreated.Reinfections with same or different serovars are common.The long-term consequences of recurrent or persistent chlamydial infections are severe leading to structural damage of the inflamed tissue.Chronic C. trachomatis infection in women has been linked with ectopic pregnancy and TFI.Animal models for chlamydial infections have shown that CD4+ Tcells are the key players both in resolution of and protection from chlamydial infection, but have been implicated also in the pathogenesis of the disease sequelae.Generation of pathologic changes in the fallopian tube tissue is mostly an unknown process but is thought to be due to repeated or persistent infections.In addition, a balance of pro-and anti-inflammatory cytokines, especially that of interferon-gamma (IFN-g) and interleukin-10 (IL-10) may have an important role during both primary and recurrent or persistent infection.We established C. trachomatis-specific T-lymphocyte lines (TLLs) and T-lymphocyte clones (TLCs) from the obstructed fallopian tube tissue specimens of infertile women (TFI) and from endometrial biopsies of patients with acute pelvic inflammatory disease.CMI responses of isolated T-cells in response to chlamydial elementary body (EB) antigens and CHSP60 were measured using lymphocyte proliferation (LP) assay.Frequency of CHSP60-responding T-cells was determined.Production of pro-inflammatory (IFN-g) and anti-inflammatory (IL-10) cytokines by the Chlamydia-specific TLLs and TLCs in response to recall antigens was determined.According to our results C. trachomatis-specific T-cells were frequently found in peripheral blood and in the inflamed fallopian tube tissue of TFI patients.One third of the T-cells derived from fallopian tube tissue specimens of TFI patients responded to CHSP60.We also found that CHSP60-specific T-cells produce IL-10 which may down-regulate appropriate IFN-g-mediated immune response needed for elimination of chlamydial infection.In addition, the CHSP60-specific CMI response was associated with HLA-DQA1*0102 and HLA-DQB1*0602 alleles and IL-10 -1082 AA genotype in the TFI patients.Taken together, these data suggest that the etiopathogenesis of C. trachomatis-related TFI is associated with impaired CMI response caused by CHSP60-reactive T-cells.Larger clinical and population-based follow-up studies are warranted to further evaluate the role of specific HLA class II and IL-10 geno(haplo)types in association with CHSP60-reactive T-cells in the pathogenesis of TFI.
Author: Anne Kinnunen
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Helsingin Yliopisto, Oulun Yliopisto
OpenAlex ID: W1920143568