Intradermal Granulocyte–Macrophage Colony-Stimulating Factor Alters Cutaneous Antigen-Presenting Cells and Differentially Affects Local versus Distant Immunization in Humans

We hypothesized that intradermal delivery of granulocyte–macrophage colony-stimulating factor (GM-CSF) would alter the number and differentiation state of local antigen-presenting cells and thereby alter immunization strength at that site in humans. GM-CSF or placebo was administered intradermally on consecutive days prior to contact sensitization at that site. In GM-CSF-treated skin, epidermal CD1a+S100+ Langerhans cells were reduced in number and had altered morphology, while the number of dermal CD1a+, HLA-DR+, and S100+ cells was increased. In the deep dermis CD68+ macrophages were increased. Expression of the APC activation markers CD40 and ICAM-1 was also increased in the dermis. Subjects were sensitized to DNCB through GM-CSF- or placebo-pretreated skin and to DPCP through untreated skin. Subjects immunized through GM-CSF-treated sites exhibited 64% greater elicitation responses to DNCB than placebo-treated subjects. GM-CSF-treated subjects also showed 43% lower responses to DPCP than placebo-treated subjects. The difference between DNCB (local) and DPCP (distant) responses was significantly greater for GM-CSF-treated subjects than for placebo responses (n = 8, P < 0.05). Therefore, local immunization site pretreatment with intradermal GM-CSF enhances immunization efficiency at that site.