Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation.
Freshly isolated murine epidermal Langerhans cells (LC) are weak stimulators of resting T cells but increase their stimulatory capacity 10-30-fold upon 2-3 d of culture together with other epidermal cells. This maturation of LC is mediated by two keratinocyte products. Granulocyte/macrophage colony-stimulating factor (GM-CSF) maintains viability and increases function. IL-1 alone does not keep LC alive, but when combined with GM-CSF further enhances their stimulatory activity. We have now searched for a cytokine that would keep LC in a viable, but functionally immature state. When LC (enriched to greater than 75%) were cultured in the presence of GM-CSF (2 ng/ml) or murine (TNF-alpha) (plateau effect at 62 U/ml), the recovery of viable LC after 72 h was identical. The LC cultured in murine TNF-alpha, however, were 10-30 times less active in stimulating resting T cells. A series of experiments demonstrated that this phenomenon was not due to the induction of insufficient amounts of GM-CSF, the induction of a suppressor factor, or a toxic effect of TNF-alpha. Interestingly, the observed TNF-alpha activity exhibited a species preference, as human TNF-alpha was not active at comparable doses. We have observed an unexpected effect of TNF-alpha on LC in vitro. Though we found that freshly prepared epidermal cells express TNF-alpha mRNA, further studies are needed to establish whether TNF-alpha plays a role in vivo by keeping resident LC in a viable, but functionally immature state.
Koch
F
F
Department of Dermatology, University of Inssbruck, Austria.
Heufler
C
C
Kämpgen
E
E
Schneeweiss
D
D
Böck
G
G
Schuler
G
G
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016207:Cytokines; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007106:Immune Sera; D007801:Langerhans Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007106:Immune Sera; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor