Influence of microenvironmental factors on human Langerhans cell function in vitro.
When murine epidermal cells are placed in tissue culture for 48-72 hr, the Langerhans cell subpopulation acquires a markedly enhanced capacity to activate autologous as well as allogeneic T cells. This change is mediated largely, if not exclusively, by GM-CSF derived from keratinocytes present in the same cultures. When human epidermal cells are cultured under similar conditions, Langerhans cells display much more limited functional changes. We have investigated whether the relative failure of human Langerhans cells to change their functional program in vitro is due to (a) production of prostaglandins by keratinocytes during functional assays (which would inhibit T cell proliferation), and/or (b) relative deficiency of GM-CSF in the 72-hr epidermal cell culture. Freshly procured and cultured (72 hr) human epidermal cells were used as stimulators for allogeneic T cells in cultures to which indomethacin was added to block prostaglandin production. Under these circumstances, the allostimulatory capacity of cultured cells was enhanced, although there was no significant increase in the stimulatory properties of fresh cells, implying that prostaglandins may account in part for the relatively poor antigen presenting properties of cultured human cells. In addition, human epidermal cells were cultured with or without exogenous GM-CSF prior to being used as stimulators for autologous and allogeneic T cells. Following exposure to GM-CSF, cultured human epidermal cells acquired markedly enhanced T cell-activating properties, rivaling those reported for cultured murine epidermal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Demidem
A
A
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Taylor
J R
JR
Grammer
S F
SF
Streilein
J W
JW
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D016212:Transforming Growth Factor beta; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016572:Cyclosporine; D007213:Indomethacin