Modulation of MHC class II+ Langerhans cell numbers in corticosteroid treated epidermis by GM-CSF in combination with...

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 candidates for vaccine development. Identification of factors which could lead to increased numbers of DC in tissues could affect immune responses by modulating their interaction with antigen which penetrates the 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 steroid depletion of Langerhans cells (LC) from the epidermis. Cytokines diluted in serum-containing medium were compared with cytokines diluted in albumin-containing, serum-free medium in order to determine a minimum 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 were effective unless they were combined with each other. In the presence of serum the combination of GM-CSF with TNF-alpha was ineffective. The data support the hypotheses that GM-CSF and TNF-alpha are both important in regulating LC numbers in the epidermis in vivo. Serum may modulate how each of these cytokines, separately or in combination, affect LC frequency in the epidermis - GM-CSF and TNF-alpha separately probably interact with other factors present in serum to increase LC frequency, 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.