Human peripheral and gastric lymphocyte responses to Helicobacter pylori NapA and AphC differ in infected and uninfected individuals.

BACKGROUND: In this study, we identify the nature of the immunological response of human peripheral blood mononuclear cells (PBMC) and lamina propria gastric lymphocytes (LPL) to two Helicobacter pylori antigens, the neutrophil activating protein (NapA) and alkyl hydroperoxide reductase (AphC). These antigens were identified and selected for study based on the observation that serological recognition of these proteins was associated with H pylori negative status in humans. AIMS: The aim was to study the serological, proliferative, and cytokine responses of PBMC and LPL, obtained from H pylori infected and uninfected individuals, to these antigens. METHODS: Patient serum, PBMC, and LPL were used to determine antibody isotype, and proliferative and cytokine responses to recombinant forms of NapA and AphC using western blotting and ELISA. RESULTS: Western blotting revealed antibody reactivity to recombinant NapA and AphC among the H pylori negative population studied. Both the proliferative and interferon gamma responses of PBMC and LPL to NapA and AphC were significantly higher in H pylori negative compared with H pylori positive subjects. Analysis of the IgG subclass profiles to both antigens revealed a T helper 1 associated IgG3 antibody response in uninfected individuals. However, interleukin 10 production was greater in H pylori positive individuals in response to these antigens. CONCLUSIONS: Taken together these data are consistent with an immune response to these antigens skewed towards a T helper 1 response in the uninfected cohort.

Placentally derived prostaglandin E2 acts via the EP4 receptor to inhibit IL-2-dependent proliferation of CTLL-2 T cells.

A number of immunomodulatory molecules are present in the placenta, including cytokines, prostaglandins, progesterone and indoleamine 2,3-dioxygenase. An undefined factor capable of down-regulating T-cell activity has recently been reported [1] as being produced by short-term cultures of placental fragments. By careful repetition of these studies we have confirmed that chorionic villi isolated from term placenta produce a low molecular weight, heat stable factor capable of inhibiting the IL-2-dependent proliferation of mouse CTLL-2 cells. This activity was not due, however, to a previously unknown immunosuppressive molecule, but rather to prostaglandin E2 (PGE2). Expression of cyclooxygenase (COX)-2 was detected in the syncytiotrophoblast of chorionic villi explants using immunohistochemistry. Culture of the explants in the presence of the COX-1/COX--2 inhibitors indomethacin and diclofenac, or with the COX-2-selective inhibitor DFP, blocked the production of the immunosuppressive factor. The immunosuppressive activity was restored by adding PGE2 to the supernatants obtained from diclofenac-inhibited explants. A number of different receptors are involved in mediating the biological effects of prostaglandins. By utilizing selective antagonists of individual receptors, we have established that the immunosuppressive effect of PGE2 on CTLL-2 cells is exerted via the EP4 receptor. Thus, addition of an EP4-selective antagonist, but not of EP1 or EP3 antagonists, abolished the immunosuppressive effect of PGE2 on CTLL-2 cells. This may have implications for attempts to selectively manipulate T-cell responses.