SUMMARYNatural killer (NK) cells are an important component of the immediate immune response to infections, including infection by intracellular bacteria. We have investigated recognition of Chlamydia trachomatis (CT) by NK cells and show that these cells are activated to produce interferon (IFN)-g when peripheral blood mononuclear cells (PBMC) are stimulated with CT organisms. Furthermore, infection of epithelial cell lines with CT renders them susceptible to lysis by human NK cells. Susceptibility was observed 18-24 h following infection and required protein synthesis by the infecting chlamydiae, but not by the host cell; heat or UV inactivated chlamydiae did not induce susceptibility to NK cell lysis. CT infection was also shown to decrease the expression of classical and non-classical major histocompatibility complex (MHC) molecules on infected cells, thus allowing recognition by NK cells when combined with an activating signal. A candidate activating signal is MICA/B, which was shown to be expressed constitutively on epithelial cells.

Using T-cell clones derived from patients with Chlamydia trachomatis (CT)-induced reactive arthritis, we identified target antigens and mapped the peptide epitopes that were recognized. Several epitopes were conserved in homologous proteins of Chlamydia pneumoniae (CPN), and it was shown that these epitopes were generated following processing of the CPN proteins or CPN elementary bodies, i.e. the T-cell clones were indeed CT and CPN cross-reactive. Given that CPN infection is frequent, we wished to determine whether prior infection with CPN could have an effect on the response to subsequent infection with CT. First, we showed that the CPN antigen, OmcB, was recognized by polyclonal peripheral blood T cells from additional subjects with CT-induced reactive arthritis; they were chosen to be HLA-DR-matched with the T-cell clones used to map epitopes in OmcB. Responses to a peptide previously shown to be conserved in CT and CPN OmcB were also seen, but only in CPN-seropositive individuals. These subjects also produced interferon-gamma (IFN-gamma) in response to CPN OmcB, and did not recognize a nonconserved epitope in OmcB. Secondly, OmcB-responsive clones from CPN-seropositive subjects were dominated by those recognizing the cross-reactive epitope, despite the recent exposure of these subjects to CT. Lastly, healthy CPN-seropositive subjects, without evidence of exposure to CT, showed greater responses, measured as IFN-gamma secretion, to CT proteins in vitro than those shown by seronegative subjects. This is consistent with the idea that prior CPN infection primes a Th1 T-cell response to CT antigens. This finding is relevant to the pathogenesis of the sequelae of CT infection (trachoma, infertility and arthritis), which may be influenced by prior exposure to CPN, and to the choice of CT antigens as vaccine candidates.

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