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 and 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-2a). Because induction of immunity to S1509a requires exposure 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. Naive CAF1 (H-2a/d) mice could be immunized against S1509a by injection with GM-CSF-exposed and TAA-pulsed epidermal cells (EC) as assessed by inhibition of the growth of inoculated tumor cells. Incubation of EC in IL-10 before GM-CSF exposure completely inhibited Ag presentation 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 ability of IL-10 to modulate EC presentation of TAA for a secondary immune response was also examined. EC were pulsed with TAA in vitro and then 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 delayed-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 after 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 tumor immune responses. IL-10 appears to specifically prevent the GM-CSF-induced maturation of LC Ag-presenting function when treatment with IL-10 occurs before exposure to GM-CSF but does not reverse the established mature state.
Beissert
S
S
Massachusetts General Hospital/Harvard Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital-East and Harvard Medical School, Charlestown 02129.
Hosoi
J
J
Grabbe
S
S
Asahina
A
A
Granstein
R D
RD
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured / Q000276:immunology
D000951:Antigens, Neoplasm; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor