Epidermal Langerhans cells from mice bearing a granulocyte macrophage-colony stimulating factor-producing mammary...

A progressive depression of delayed type hypersensitivity reactions occurs during development of mammary tumors in BALB/c mice. This tumor constitutively produces prostaglandin E2 (PGE2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Epidermal Langerhans cells were found to have a decreased responsiveness to bacterial superantigen and to defined antigens in tumor-bearing mice, and also showed an impaired ability to induce proliferative responses in syngeneic or allogeneic responder T cells. Flow cytometric analysis revealed that the Langerhans cells of tumor bearers had decreased densities of the Ia molecule on their surfaces. No defects were observed in the potential of keratinocytes from tumor bearers to produce granulocyte-macrophage colony stimulating factor or to support the activation of syngeneic T cells. Incubation of normal Langerhans cells with tumor derived factors depressed their capacity to stimulate T cell syngeneic responses. Addition of indomethacin and anti-prostaglandin E2 did not reverse this depressed activity. These results indicate that epidermal Langerhans cells from tumor-bearing mice possess a functional deficit in acquiring accessory properties in vitro, which cannot be ascribed to a lack of GM-CSF in the local microenvironment or to production of inhibitory cytokines by their keratinocytes. The functional deficit of epidermal Langerhans cells of tumor-bearing mice may account for the depressed delayed hypersensitivity displayed by these mice, and factors elaborated by the tumor may be responsible for the deficiencies observed.