Differential regulation of human T cell responsiveness by mucosal versus blood monocytes.
Human intestinal T lymphocytes are constantly exposed to a large number of foreign antigens without developing a systemic immune response. One crucial mechanisms 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 addressed the question whether a lack of co-stimulatory/progression signals might also contribute to LP-T hyporesponsiveness. To this end, isolated 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 macrophages (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 accessory receptors CD11/18, CD2 and CD28/CTLA-4 on mucosal macrophages. Thus, down-regulation of both recognition/competence and co-stimulatory/progression signals contribute to intestinal hypo- or unresponsiveness.
Qiao
L
L
Abteilung für Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Braunstein
J
J
Golling
M
M
Schürmann
G
G
Autschbach
F
F
Möller
P
P
Meuer
S
S
D000941:Antigens / Q000276:immunology; D001769:Blood / Q000276:immunology; D002478:Cells, Cultured; D003106:Colon; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000145:classification / Q000276:immunology*; D009928:Organ Specificity; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000941:Antigens; D017260:Receptor-CD3 Complex, Antigen, T-Cell