DIFFERENTIAL REGULATION OF HUMAN T-CELL RESPONSIVENESS BY MUCOSAL VERSUS BLOOD MONOCYTES

Human intestinal T lymphocytes are constantly exposed to a large numbe r of foreign antigens without developing a systemic immune response. O ne crucial mechanism leading to this intestinal hyporesponsiveness is based on impaired signal transduction through the T cell receptor/CD3 complex in lamina propria T lymphocytes (LP-T). In this study, we addr essed the question whether a lack of co-stimulatory/progression signal s might also contribute to LP-T hyporesponsiveness. To this end, isola ted human monocyte populations from the intestinal lamina propria were obtained and their phenotypes as well as their capacity to promote T cell activation studied. Here, we demonstrate that lamina propria macr ophages (LP-MO), in contrast to peripheral blood monocytes (PB-MO), do not support proliferation of either LP-T or PB-T. This may be due to the low expression of ligands (CD54, CD58, CD80) for the T cell access ory receptors CD11/18. CD2 and CD28/CTLA-4 on mucosal macrophages. Thu s. down-regulation of both recognition/competence and co-stimulatory/p rogression signals contribute to intestinal hypo- or unresponsiveness.