IL-10 INHIBITS TUMOR-ANTIGEN PRESENTATION BY EPIDERMAL ANTIGEN-PRESENTING CELLS

IL-10 inhibits Langerhans cell (LC) Ag presentation to Th1 clones. As LC are capable of presenting tumor-associated Ags (TAA) for primary an d secondary tumor immune responses, we examined the effect of IL-10 on LC Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2(a)). Because induction of immunity to S1509a requires expos ure of LC to granulocyte-macrophage (GM)-CSF, this system also allowed us to study the regulatory interactions of GM-CSF and IL-10 on LC. Na ive CAF(1) (H-2(a/d)) mice could be immunized against S1509a by inject ion with GM-CSF-exposed and TAA-pulsed epidermal cells (EC) as assesse d by inhibition of the growth of inoculated tumor cells. Incubation of EC in IL-10 before GM-CSF exposure completely inhibited Ag presentati on in this system. Significantly, neither co-incubation of EC in IL-10 and GM-CSF (without preincubation in IL-10) nor IL-10 treatment after GM-CSF incubation was able to exert a down-regulatory effect. The abi lity of IL-10 to modulate EC presentation of TAA for a secondary immun e response was also examined. EC were pulsed with TAA in vitro and the n injected into a hind footpad of tumor-immune mice with 24 h swelling assessed as a measure of delayed-type hypersensitivity. Preincubation in IL-10 before TAA exposure significantly inhibited elicitation of d elayed-type hypersensitivity with or without subsequent exposure to GM -CSF. Co-incubation of EC in IL-10 and GM-CSF or exposure to IL-10 aft er GM-CSF led to a normal response. These data indicate that IL-10 may serve as an important regulator of LC Ag-presenting function for tumo r immune responses. IL-10 appears to specifically prevent the GM-CSF-i nduced maturation of LC Ag-presenting function when treatment with IL- 10 occurs before exposure to GM-CSF but does not reverse the establish ed mature state.