F. Fändrich¹, J. Schröder¹, T. Jahnke¹, A.M. Waaga³, M.R. Pawaresch², H.H. Wacker²

¹Dept. of General & Thoracic Surgery and ²Institute of Pathology, University of Kiel, Germany.
³Brigham and Women's Hospital, Harvard Medical School, Boston, MA, U.S.A.

Received 12/2/96; Accepted 12/18/96; On-line 01/01/97

INTRODUCTION

One major mechanism in the inititiation of allogeneic organ rejection is mediated by specialized antigen-presenting cells within the gut associated lymphatic tissues (GALT). Besides the commonly described professional antigen presenting cells (APCs) like Langerhans cells, veiled dendritic cells, and interdigitating dendritic cells, there are two unique forms of dendritic cells - namely sinus lining cells (SLCs) and follicular dendritic cells (FDCs) - which effectively contribute to the process of humoral immune responses (1). SLCs, also designated as antigen transport cells (ATCs) (2,3), derive from bone marrow precursors (monocytes) (1,2) and are preferentially localized within the marginal and interfollicular sinus of lymph nodes and the marginal zone of the spleen. Here, their main function is to capture soluble antigen and particulate material which enters the afferent lymphatic vessels. After endocytosis of exogenous antigen, fragmented molecules are loaded as peptides into major histocompatibility complex (MHC) class-II specific molecules. Following antigen expression on their cell surface, SLCs migrate to the B cell dependent areas of lymph nodes, spleen, and Peyer's patches where they give rise to the differentiation of follicular dendritic cells and germinal center formation (4). In contrast to SLCs, FDCs preferentially present native antigen in the form of antigen-antibody-complexes which are retained in immunogenic form on their cell membranes to mediate antibody responses to exogenous antigens via B-cell proliferation. FDCs are non-phagocytic specialized dendritic cells which stimulate secondary humoral immune responses, including the clonal proliferation of memory B cells (5). It has been demonstrated that activated B-cells bind to FDCs, a process which is dependent on the interaction of cell surface adhesion molecules in addition to antigen contact (6). As FDCs are well endowed with complement receptors of all three types, they are able to target large amounts of immune complexes which continue to stimulate B-cells (7). The continuous antigen presentation in close proximity to B-cells is required for the formation of secondary germinal centers and the maintenance of immunological memory (8).

Following small bowel transplantation, a large number of donor-derived immunocompetent effector cells invade the lymphatic tissues of the host. Under circumstances where the host's immune defense mechanisms are compromised, host-specific effector cells of the graft are able to trigger a lethal graft-versus-host reaction (GvHR). In this study, a graft-versus-host model was established between inbred rat strains and heterotopic small bowel transplantation (HSBTx) was performed. The established graft-versus-host model was chosen to investigate the role of SLCs and FDCs in a one-sided rejection model, where immunocompetent cells of donor and recipient lymphatic tissues were supposed to demonstrate different migration and proliferation patterns due to a different recognition mechanism between parental and F1-hybrid derived immunocompetent cells. In this context, we hypothesized that 15-deoxyspergualin (15-DOS) which has been shown to suppress primary and secondary responses to thymic dependent and independent antigens (9) would be effective to sustain an unaltered functional and anatomical compart-mentalization of the B-cell associated units of lymphatic organs during the course of a graft-mediated anti-host immune attack.