The Frequency ofChlamydia trachomatisMajor Outer Membrane Protein-Specific CD8⁺T Lymphocytes in Active Trachoma Is Associated with Current Ocular Infection

Abstract

Chlamydia-specific cytotoxic T lymphocytes are able to control model infections but may be implicated in disease pathogenesis. HLA-A2 peptide tetramers to Chlamydia trachomatis major outer membrane protein 258-266 (MOMP258-266) and MOMP260-268 were used to characterize HLA class I-restricted CD8 ؉ T cells in Gambian children aged 4 to 15 years with clinical signs of active trachoma and/or infection with C. trachomatis. The frequencies of circulating HLA-A2 tetramer binding cells (TBC) were determined in whole blood samples by flow cytometric analysis. Initial screening of subjects with an anti-HLA-A2 antibody confirmed the presence of either HLA-A2 or HLA-A28. These were subsequently further divided by molecular subtyping. The C. trachomatis-specific HLA-A2 peptide tetramers were able to bind T cells with receptors from subjects which were restricted by either the HLA-A2 or the HLA-A28 restriction element. In this population, the median value of C. trachomatis-specific CD8 ؉ T cells was 0.02%, with frequencies of up to 3.71% of CD8 ؉ T cells reactive with a single tetramer in a minority of subjects. TBC were detected more often in subjects who were infected at the ocular surface, and their presence was associated with infection episodes of longer duration. Detection of C. trachomatis-specific TBC was not associated with the presence of disease or with the estimated load of ocular C. trachomatis infection at the time of sample collection. High frequencies of C. trachomatis-specific cells did not predict subsequent appearance or resolution of the clinical disease signs of active trachoma.

The effect of Chlamydophila pneumoniae Major Outer Membrane Protein (MOMP) on macrophage and T cell-mediated immune responses

“…Conversely, we found that MOMP had no effect on the expression of CD40L in CD8 + T cells suggesting once more a selective effect of MOMP on T-helper-mediated immune responses. Our result contrast with previous findings showing that MOMP or MOMP-derived peptides significantly increase the proliferation of antigen-specific CD8 + T cells in vivo (Kim et al 1999;Rodriguez et al 2006;Holland et al 2006;Mahdi et al 2001) suggesting the participation of other antigen presenting cells and components of the immune response that may be absent in our in vitro setting and that could play a key role in the induction of CD8 + T cell responses in vivo.…”

Protective Immunity toChlamydia trachomatisGenital Infection: Evidence from Human Studies

“…These findings were then applied to a clinical study of trachoma where the frequency of MOMP-specific CD8+ T lymphocytes in peripheral blood were sought. Frequency of these cells correlated with active ocular infection, but sample sizes were too small to relate to protection or disease outcome [74]. …”

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

“…Indeed, peptides derived from chlamydial proteins are known to be presented by MHC class I molecules (reviewed in reference 1) and Chlamydia-reactive CD8 ϩ T cells have been detected in patients (2,3). Despite the presence of antigen-specific T cells, infection with Chlamydia trachomatis can cause serious diseases in humans.…”