Functional and Applied Anatomy
Centrum Anatomy 4120
Hannover Medical School
Carl-Neuberg.Str.1
30625 Hannover

Lymph nodes are key players in the induction of immune responses. Antigens are transported by dendritic cells (DC) or as soluble molecules via the afferent lymphatics into the draining lymph node (LN), where an acquired immune response is initiated. Antigen presentation begins which is associated with several alterations of subset composition and the pattern of cytokine and chemokine production within the microenvironment of the draining LN. The extent of an acquired immune response within the draining LN is dependent on the site of antigen application and the amplitude of the antigenic stimulus in the draining area. In addition, it is important which DC are available and which cytokines are produced during the immune response in the microenvironment of the draining LN. In recent studies it was shown that the microenvironment of the mesenteric lymph node (mLN) is different from that of the peripheral lymph node (pLN). Therefore, it will be studied under normal and pathological conditions how the microenvironment and the function of the mLN are influenced by their drained area, the gut.

Therefore rat mLN will be removed and a fragment of a lymph node which differs in respect to its drained area, e.g. the pLN, will be transplanted in this region. It is known that transplanted fragments leads to functionally intact lymphatic tissue. During the reconstitution of the lymph node it will be observed, how the drained area affects the subset of the transplanted fragment, the structure of compartments, the DC network and the cytokine response.

It is known that effector T cells, which were stimulated in the microenvironment of the mLN, preferentially accumulated again in the mLN after re-circulation. We showed that mLN effector T cells preferentially survive in the microenvironment of mLN in response to the cytokine pattern of the mLN. Therefore, the survival of injected mLN effector T cells will be analysed in the transplanted fragments. From this it will be elucidated how the microenvironments of the transplanted fragments influence the survival of effector T cells. In addition, the function of the transplanted fragments will be measured under pathological conditions (an Indomethacin-induced ileitis in rats). These tests will clarify how the afferent lymphatics are involved in gut immune responses. After establishing the model in the rat system we also want to analyse specific functions of single cell types in the mouse system, defining the importance by using knock out animals.