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 >75%) were cultured in the presence of GM-CSF (2 ng/ml) or murine (TNF-α) (plateau effect at 62 U/ml), the recovery of viable LC after 72 h was identical. The LC cultured in murine TNF-α, 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-α. Interestingly, the observed TNF-α activity exhibited a species preference, as human TNF-α was not active at comparable doses. We have observed an unexpected effect of TNF-α on LC in vitro. Though we found that freshly prepared epidermal cells express TNF-α mRNA, further studies are needed to establish whether TNF-α plays a role in vivo by keeping resident LC in a viable, but functionally immature state.