The migration of Langerhans’ cells into and out of lymph nodes draining normal, carcinogen and antigen‐treated sheep skin

Abstract

Summary Epidermal Langerhans' cell (LC) migration to the regional lymph node and beyond into central lymph was examined in sheep following topical application of the complete chemical carcinogen 7,12-dimethylbenz(a)anthracene(DMBA) or the contact sensitizing antigen 2,4,6-trinitrochlorobenzene (TNCB). This was facilitated by cannulating previously constructed pseudoafferent lymphatic vessels draining the skin treated with these agents or alternatively, the efferent lymphatic vessel of the regional lymph node.Application of DMBA resulted in a biphasic increase in LC migration. There was an initial increase in LC migration at 25 h with the maximum response (3.6 x 10^ LC/h) occurring approximately 5 days after DMBA treatment. In contrast, the contact sensitizing antigen TNCB caused enhanced LC migration within mitiutes of the application of antigen (3.3 x 10'' LC/h) and peak migration at 8-12 h.Examination of efferent lymph cells from the regional lymph node after DMBA treatment showed uncharacteristically large numbers of LC traversing the lymph node. These LC migration patterns suggest ditferent mechanisms may trigger the migration of LC from skin after the application of DMBA to those associated with the normal processes of antigen presentation.

B Cell-Driven Lymphangiogenesis in Inflamed Lymph Nodes Enhances Dendritic Cell Mobilization

“…Typically, approximately only 0.1% of the efferent lymphatic output is comprised of DCs or macrophages (Anderson et al, 1981;Bell, 1979), even after stimulation of DC migration with contact sensitizers (Dandie et al, 1994). When we collected efferent lymph at the cysterna chyli (Matloubian et al, 2004) after FITC application to the entire lower body of nonimmunized mice, we were unable to detect more than 0.1% FITC + CD11c + DCs in efferent lymph (data not shown).…”

Inflammation, Lymphatic Function, And Dendritic Cell Migration

“…For example, intradermal immunization of rabbits with alum-precipitated diphtheria toxin induces a progressive increase in the number of DCs in afferent lymph, peaking at 4 to 5 days after immunization. 45 Topical application of the contact sensitizer 2,4,6-trinitrochlorobenzene (TNCB) increases the input of Langerhans cells in afferent lymph, 46 peaking after 5 days, consistent with the depletion of Langerhans cells in skin and the delayed accumulation of these DCs in draining LNs observed after FITC application. 47 A more dramatic effect is observed after topical application of the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA).…”

Dynamic accumulation of plasmacytoid dendritic cells in lymph nodes is regulated by interferon-β

“…[14][15][16] In the case of cDCs, it is generally accepted that these cells die in the LNs after antigen presentation to T cells, but that in some cases cDCs can exit LNs through efferent lymphatics. 37 Indeed, CD11c ϩ DCs have been detected in thoracic duct preparations in mice, 38 sheep, 39 and rats, 40,41 and technical limitations could arguably underestimate the numbers of DCs in efferent lymph. Because the retention of lymphocytes in LNs is dependent on engagement of S1P receptors, in particular S1P1 for lymphocytes, 2 we reasoned that pDCs may also be sensitive to retention signals to optimize their transit time through the LNs.…”