TUMOR NECROSIS FACTOR a MAINTAINS THE VIABILITY OF MURINE EPIDERMAL LANGERHANS CELLS IN CULTURE, BUT IN CONTRAST TO GRANULOCYTE/MACROPHAGE COLONYSTIMULATING FACTOR, WITHOUT INDUCING THEIR FUNCTIONAL MATURATION

Dendritic cells (DC) 1 are class II-positive leukocytes specialized to initiate primary T cell-dependent immune responses (1-3) . DC were first identified in lymphoid tissues, and'most of the studies that have unraveled their unique stimulatory capacity for resting T cells used DC isolated from lymphoid organs . New insight into the biology of DC came from studies of murine epidermal Langerhans cells (LC) in vitro (4-14) . These studies suggest that LC in the skin and possibly DC in other nonlymphoid tissues as well represent precursors or immature elements of the DC system (15, 16). Resident LC constitutively express class II MHC antigens, but are only weak stimulators of resting T cells when isolated from the skin . During 2-3 d of bulk epidermal cell (EC) culture, however, LC increase their sensitizing activity for resting T cells 10-30-fold, and come to resemble lymphoid DC in morphology and surface markers as well (4). Granulocyte/macrophage colonystimulating factor (GM-CSF) was identified as the principal mediator of this LC maturation in vitro (6, 7) . GM-CSF maintains LC viability and increases function, whereas IL-1 enhances LC function twofold when combined with GM-CSF but does not support viability by itself (7). As LC in situ are immature but presumably long-lived (17-19), we have now searched for a cytokine that would keep LC alive without inducing their functional maturation . Among apanel of purified cytokines tested, only TNFa exhibited this activity. This finding reveals yet another facet of this pleotropic mediator (20, 21). Whether TNFa plays any physiological role in LC homeostasis is unknown at present, but appears possible as we found TNFct mRNA in freshly prepared EC.