Characterisation of immune responses during sexually transmitted infections
Over the years, the scientific community has proposed the development of vaccines to confer protection against STIs. These vaccines aim to elicit mucosal immune responses in the female reproductive tract and generate localised memory at sites of potential exposure to better control infection. However, limited access to mucosal tissues in women has hampered the ability to accurately measure immune responses. The EU-funded FRT-HOMING (Identifying new markers and homing profiles involved in lymphocyte migration to the female reproductive tract) project proposed to develop assays that indirectly measure antigen-specific T cell responses. Researchers were particularly interested in defining the homing profile of lymphocytes migrating to the female genital. Towards this goal, they investigated adhesion molecules expressed on effector T cells during genital tract infection as surrogate markers of genital tract immunity. The FRT-HOMING working hypothesis was that lymphocytes induced as a result of reproductive tract immunisation or infection, traffic transiently in the blood, expressing a specific set of homing markers. The consortium worked to identify specific integrins and homing receptors expressed on circulating lymphocytes that direct their migration to the female reproductive tract. Scientists isolated cells from blood shortly after mucosal immunisation or infection in animal models and patients, and performed gene expression analysis. In a mouse model of vaginal infection with Chlamydia, researchers discovered an upregulation of specific chemokine receptors such as CCR2, CCR5, CXCR6 and the integrin CD11c in effector T cells. A similar profile was observed in women specifically suffering from bacterial vaginosis but not during other skin or gut inflammatory conditions. Importantly, expression of CD11c distinguished a population of circulating T cells with innate capacity and mucosal homing potential. Collectively, the activities of the FRT-HOMING study demonstrated the possibility of measuring T cells expressing CD11c in blood as an indicator of T cell immunity in the female genital tract. This can serve as a promising tool for vaccine development and as a target for eliciting protective immunity against STIs.
Keywords
Sexually transmitted infections, FRT-HOMING, T cell, CCR5, CD11c