EPIDERMAL LANGERHANS-CELLS FROM MICE BEARING A GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR-PRODUCING MAMMARY-TUMOR DISPLAY IMPAIRED ACCESSORY FUNCTIONS

A progressive depression of delayed type hypersensitivity reactions oc curs during development of mammary tumors in BALB/c mice. The tumor co nstitutively produces prostaglandin E(2) (PGE(2)) and granulocyte macr ophage colony stimulating factor (GM-CSF). Epidermal Langerhans cells were found to have a decreased responsiveness to bacterial superantige n and to defined antigens in tumor-bearing mice, and also showed an im paired ability to induce proliferative responses in syngeneic or allog eneic responder T cells. Flow cytometric analyses revealed that the La ngerhans cells of tumor bearers had decreased densities of the la mole cule on their surfaces. No defects were observed in the potential of k eratinocytes from tumor bearers to produce granulocyte macrophage colo ny stimulating factor or to support the activation of syngeneic T cell s. Incubation of normal Langerhans cells with tumor derived factors de pressed their capacity to stimulate T cells syngeneic responses. Addit ion of indomethacin and anti-prostaglandin E(2) did not reverse this d epressed activity. These results indicate that epidermal Langerhans ce lls from tumor-bearing mice possess a functional deficit in acquiring accessory properties in vitro, which cannot be ascribed to a lack of G M-CSF in the local microenvironment or to production of inhibitory cyt okines by their keratinocytes. The functional deficit of epidermal Lan gerhans cells of tumor-bearing mice may account for the depressed dela yed hypersensitivity displayed by these mice, and factors elaborated b y the tumor may be responsible for the deficiencies observed.