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Published online before print June 12, 2007

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(Journal of Leukocyte Biology. 2007;82:795-800.)
© 2007 by Society for Leukocyte Biology

The impact of cell-bound antigen transport on mucosal tolerance induction

Institute of Immunology, Hannover Medical School, Hannover, Germany

¹ Correspondence: Institute of Immunology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. E-mail: pabst.oliver{at}mh-hannover.de

Mucosal surfaces are exposed continuously to a flood of foreign antigens demanding a tightly controlled balance between immunity and tolerance induction. Tolerance toward food and inhaled antigens, known as oral and respiratory tolerance, respectively, evokes a body-wide nonresponsiveness against the plethora of environmental antigens. Key issues in understanding the induction of mucosal tolerance relate to the site of antigen entrance, the mechanisms of antigen transport, and the exact anatomical location where lymphocytes meet their cognate antigens. In this regard, opposing ideas have been put forward: In one scenario, antigens taken up at mucosal surfaces are considered to spread throughout the body, thus potentially evoking tolerogenic immune responses in all secondary lymphoid organs. Alternatively, tolerance induction might be confined to the draining regional lymph nodes (LN). Recent observations strongly supported the latter scenario, emphasizing the importance of regional LN and their network of afferent lymphatics in this process. In this model, air-borne and intestinal antigens are captured at mucosal sites by dendritic cells, which then migrate exclusively in a CCR7-dependent way to draining regional LN. Tolerance is then induced actively by the activation of antigen-specific T cells, which are subsequently deleted, become anergic, or alternatively, differentiate into regulatory T cells. Thus, the concept of local induction of immune responses seems to hold true for the majority of immune reactions, regardless of whether they are tolerogenic or defensive in their outcome.

Key Words: oral tolerance • CCR7 • intestine • lung • antigen presentation

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