The Concept of Migration Dependent Dendritic Cell Activation

Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells (APCs) (1). The function of DCs depends on their maturation stages: progenitors in the bone marrow, precursors in the blood, immature DCs in peripheral tissues, antigen-transporting DCs in the afferent lymphatics, and

From: The Receptors: The Chemokine Receptors Edited by: J. K. Harrison and N. W. Lukacs © Humana Press Inc., Totowa, NJ

mature APCs in lymph nodes (LNs) (2). In a steady-state life cycle, a small number of DCs continually scans self-components at peripheral tissues and maintains peripheral tolerance to self after migrating to LNs (3). When exposed to danger signals, accelerated traffic of DCs occurs, and these newly recruited DCs strongly promote cell-mediated immunity in LNs (4-7). This trafficking pattern is quite distinct from that of T lymphocytes, which continually circulate from blood to LNs via high endothelial venules (HEVs). Naïve lymphocytes are exposed to antigens presented by DCs in the LNs, leading to their proliferation and differentiation into appropriate memory/primed T cells. Primed T cells exit the LNs and recirculate to home to peripheral tissues. It is well established that LNs are induction sites whereas peripheral tissues are effector sites for T cells. In this review, we propose novel concepts that LNs are effector sites whereas peripheral tissues are induction sites for DCs and that DCs are also classified by naïve, primed, and effector stages depending on the anatomical positioning (Fig.1). Because DCs encounter and ingest self or nonself antigens

Fig. 1. A model for functional migration of DCs and T cells. DCs are classified into naïve, primed, and effector DCs, DCpre, and DC precursor. pMHC, peptide-major histocompatibility complex.

initially in peripheral tissues, the bone marrow, blood, and tissue DCs before encountering antigens are characterized as naïve DCs. Once recognizing and processing peripheral antigens, naïve DCs upregulate cell-surface peptide-MHC complex to become primed DCs, which locate within peripheral tissues, afferent lymphatics, and LNs. Finally, primed DCs acquire antigen-presenting ability to naïve T lymphocytes in T-cell zones of LNs. Because the most important effector function for DCs is antigen presentation, we call these fractions effector DCs. Effector DCs flexibly determine the type of immune responses in the LNs by summing up the information that they obtain from tissue environments and exogenous factors.

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