Projekt: Characterization of human peripheral and intestinal T cell responses after mucosal antigen exposition: Induction of tolerance vs. immunity

Titel: Characterization of human peripheral and intestinal T cell responses after mucosal antigen exposition: Induction of tolerance vs. immunity

Supervisor:
Dr. Reiner Ullrich (Project A14)
Medizinische Klinik I
Charité, CBF

Contact: ullrich@zedat.fu-berlin.de; Tel.: 8445 4351

Background information: Specific immune modulation by oral antigen in humans has been hampered so far because the effects of different oral antigen applications are not well understood and because the inductive compartments of the human mucosal immune system cannot readily be accessed. Significant progress has been achieved in these two areas during the first funding period: Using the neo-antigen keyhole limpet hemocyanin (KLH) we established an effective protocol for the detection of KLH-specific T- and B cell responses and demonstrated that a low-dose oral KLH administration modulates the subsequent immune response to parenteral KLH. In addition, a method to isolate T cells from mucosal lymphoid follicles in resected human colon was established, which allowed first functional analyses of this so far inaccessible T cell population.
Building on these achievements and in view of recent findings suggesting that antigen presentation by specific dendritic cells in mesenteric lymph nodes determines the type of immune response after oral antigen administration we will investigate mechanisms of tolerogenic immune regulation. We will study antigen-specific responses after oral antigen administration in T cells from intestinal lamina propria, mucosal lymph follicles and mesenteric lymph nodes. In addition, defects of oral tolerance induction in patients with chronic inflammatory bowel diseases will be investigated. Finally, we will try to induce tolerance by oral antigen in KLH-immune volunteers and identify the involved mechanisms.