MODULATION OF MHC CLASS II-TREATED EPIDERMIS BY GM-CSF IN COMBINATIONWITH TNF-ALPHA( LANGERHANS CELL NUMBERS IN CORTICOSTEROID)

It is important to understand how dendritic cells (DC) are recruited, maintained and stimulated to migrate from tissues to lymph nodes. This is because DC are potent initiators of primary immune responses and c andidates for vaccine development. Identification of factors which cou ld lead to increased numbers of DC in tissues could affect immune resp onses by modulating their interaction with antigen which penetrates th e tissue. To identify cytokines which could increase DC in tissues we tested the ability of GM-CSF TNF-alpha and IL-6 to partially prevent s teroid depletion of Langerhans cells (LC) from the epidermis. Cytokine s diluted in serum-containing medium were compared with cytokines dilu ted in albumin-containing, serum-free medium in order to determine a m inimum combination of cytokines required to increase LC and the effect of serum on the LC-increasing activity of cytokines. In the presence of serum, GM-CSF or TNF-alpha could increase LC frequency compared to the control; but in the absence of serum neither of these cytokines we re effective unless they were combined with each other. In the presenc e of serum the combination of GM-CSF with TNF-alpha was ineffective. T he data support the hypotheses that GM-CSF and TNF-alpha are both impo rtant in regulating LC numbers in the epidermis in vivo. Serum may mod ulate how each of these cytokines, separately or in combination, affec t LC frequency in the epidermis -GM-CSF and TNF-alpha separately proba bly interact with other factors present in serum to increase LC freque ncy, whereas in combination it is possible that these separate effects are cancelled in the presence of serum. TNF-alpha and GM-CSF together , in the absence of serum, form one combination of a minimum number of cytokines which can regulate LC frequency in the epidermis; and IL-6 alone, or in combination with GM-CSF, does not increase LC frequency.