The lymphotoxin pathway as a novel regulator of dendritic cell function

Abstract

Dendritic cells (DC) are critically required for the host response to antigen (Ag) [1, 2]. Upon exposure to antigen, DC take up Ag within the peripheral tissues and subsequently migrate in response to chemokine gradients into the lymphatics [3]. During this initial exposure to Ag, DC become activated by the sensing of microbe-associated molecular patterns (MAMPs) and consequently upregulate co-stimulatory molecules such as B7.1 and B7.2 so that they may optimally prime Ag-specific CD4 + T cells [4-6]. DC leave the tissue and enter the lymphatics where they journey to the inflamed draining lymph node (LN) [7, 8]. Upon entry into the LN via the subcapsular sinus, DC "find" rare Ag-specific CD4+ T cells by taking advantage of the intricate organization of the LN tissue itself [9]. Once DC encounter Ag-specific T cells, the T cells become activated to proliferate. These activated T cells also concurrently provide signals back to the Ag-bearing DC in a process that has been termed DC licensing. Licensed DC can then cross-prime a CD8 + T-cell response so that pathogen may be cleared. The nature of these helper T cell-derived signals and their impact on the Ag-bearing DC remain poorly elucidated. © 2011 Springer Science+Business Media, LLC.