Characterization of sheep afferent lymph dendritic cells and their role in antigen carriage.

Abstract

We have ablated peripheral lymph nodes in sheep and subsequently cannulated the pseudo-afferent lymphatic vessel that arises as a consequence of afferent lymphatic vessels reanastomosing with the former efferent duct. This technique allows the collection of lymph with a cellular composition that resembles true afferent fluid, and in particular, containing 1-10% dendritic cells. A 16-h collection of this lymph may contain between 10(6) and 10(7) dendritic cells. This dendritic cell population may be enriched to greater than 75% by a single-density gradient centrifugation step. We have generated a mAb that recognizes sheep CD1. This monoclonal not only reacts with afferent dendritic cells, but with dendritic cells in the skin and paracortical T cell areas of lymph nodes. The expression of CD1 suggests afferent dendritic cells are related to skin Langerhans' cells and other dendritic cells that act as accessory cells for T cell responses. Consistent with this is the high level of expression by dendritic cells of molecules involved in antigen recognition by T cells, including MHC class I and class II. Afferent dendritic cells express high levels of the cellular adhesion molecule LFA-3, and at the same time express a ligand for this molecule, namely CD2. The accessory functions of afferent dendritic cells resemble those displayed by mature Langerhans' cells and by lymph node interdigitating cells. These include clustering with resting T cells and stimulating their proliferation in a primary response to antigen. Afferent dendritic cells are capable of acquiring soluble protein antigen in vivo or in vitro and presenting the material directly to autologous T cells in an antigen-specific manner. We conclude that afferent dendritic cells represent a lymph-borne Langerhans' cell involved in antigen carriage to the lymph node.

Maturation and Trafficking of Monocyte-Derived Dendritic Cells in Monkeys: Implications for Dendritic Cell-Based Vaccines

“…Fossum (32) reported that purified lymph DC injected into footpads of mice mostly were retained at the site of injection. Lymph DC represent a maturing DC population (33), and hence these findings may be consistent with our results. More recently, Ag-stimulated blood-derived human DC used therapeutically in human cancer patients were only partially cleared from an i.d.…”

Dendritic cell homeostasis

“…10 Although DC efflux from tissues to the tissue-draining LN is difficult to accurately quantify, 11 it is clear that tissue-DC homeostasis requires constant replacement with new cells. BM chimera studies in mice established that kidney and heart DCs are replaced in 2 to 4 weeks after lethal irradiation and BM transplantation, whereas DC repopulation in the vagina, 12 airway epithelia, 13 and the gut is more rapid and occurs in 7 to 13 days (M. Bogunovic and M.M., unpublished data, January 2009).…”

Distribution of human colonic dendritic cells and macrophages

“…Following exposure to antigen, dendritic cells mature and develop potent immunostimulatory activity whilst migrating to draining lymph nodes; there they interact with T cells to initiate T cell responses. Thus, in various animal models, dendritic cells in the afferent lymph are associated with antigen and can initiate antigen-specific T cell-mediated responses [3,26,27].…”