Premium
Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells
Author(s) -
WANG B.,
KONDO S.,
SHIVJI G. M.,
FUJISAWA H.,
MAK T. W.,
SAUDER D. N.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.1996.tb00016.x
Subject(s) - tumor necrosis factor alpha , fluorescein isothiocyanate , receptor , biology , antigen , microbiology and biotechnology , immunology , chemistry , cancer research , biochemistry , physics , quantum mechanics , fluorescence
Summary Langerhans' cells (LC) represent the major antigen‐presenting cells within the epidermis. Following exposure of the skin to antigen, LC take up antigen, migrate into draining lymph nodes (DLN) and present processed antigen to T lymphocytes, thereby initiating an immune response. The molecular mechanisms responsible for LC migration remain unclear. Cytokines, in particular tumour necrosis factor‐α (TNF‐α) have been suggested to influence LC migration. There are two distinct membrane receptors for TNF‐α, TNF receptor I (TNF‐R1, p55) and TNF receptor II (TNF‐R2, p75), thought to be responsible for distinct TNF‐α activities. It is believed that most of TNF biological activities are mediated via TNF‐R1. In order to examine the role of TNF‐R1 signalling in LC migration, we utilized TNF‐R1 gene‐targeted mutant mice. Following application of the hapten fluorescein isothiocyanate (FITC), FITC‐bearing cells in DLN were examined by flow cytometry. A normal number of FITC + /Ia + cells (LC) were found in DLN from TNF‐R1‐deficiency mice, suggesting that TNF‐R1‐dependent signalling is not crucial for LC migration. To investigate the possibility of signalling through TNF‐R2, blocking studies using a neutralizing anti‐TNF‐α antibody were performed. The results revealed that anti‐TNF‐α antibody significantly inhibited LC accumulation in DLN in TNF‐R1‐deficient mice, thus suggesting that TNF‐R2 signalling is involved in LC migration from skin to DLN and that murine LC express TNF‐R2.