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Control of the differentiation state and function of human epidermal Langerhans cells by cytokines in vitro
Author(s) -
Prignano F,
Gerlini G,
Fossombroni V,
Pimpinelli N,
Giannotti B,
Nestle FO,
Romagnoli P
Publication year - 2001
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1046/j.1468-3083.2001.00304.x
Subject(s) - epidermis (zoology) , langerhans cell , cytokine , birbeck granules , microbiology and biotechnology , cellular differentiation , tumor necrosis factor alpha , biology , stem cell factor , stem cell , immunology , haematopoiesis , antigen , anatomy , biochemistry , gene
Langerhans cells can originate in vitro from immature precursors stimulated with granulocyte macrophage‐colony‐stimulating factor (GM‐CSF), tumour necrosis factor (TNF)‐α and stem cell factor (SCF). We asked whether these cytokines also control the differentiation state of Langerhans cells within the epidermis and upon leaving this tissue. We harvested sheets of human epidermis by controlled dispase hydrolysis of keratomes, cultured them in RPMI and 10% fetal calf serum for 48 h and analysed the sheets and the cells migrated spontaneously into the medium, most of which were Langerhans cells containing Birbeck granules. 1 By flow cytometry, the intensity of CD1a expression was reduced quite evenly among Langerhans cells migrated from sheets within 48 h. The cells in the sheets underwent loss of dendrites, with a significant reduction in the cell perimeter that was prevented by GM‐CSF and TNF‐α together. Either of these cytokines induced expression of CD18 by cells in the sheets and those in the medium. Moreover, TNF‐α induced expression of CD54 by cells in the medium, but not by those retained in the sheets, whereas human SCF induced, dose dependently, expression of CD54 by cells in the sheets, but not from those in the medium. 2 The proliferation of allogeneic lymphocytes was much higher when stimulating Langerhans cells were harvested from cultures with any cytokine, rather than from cultures without cytokines. We conclude the following: (i) GM‐CSF and TNF‐α help to maintain full differentiation of Langerhans cells within the epidermis; (ii) cytokine influence on Langerhans cells adhesiveness is in part context dependent; and (iii) pretreatment with cytokines influences positively the number or accessory activity of Langerhans cells on lymphocytes during subsequent mixed leucocyte reaction.