IMMUNE DYSFUNCTION IN EXPERIMENTAL VERSUS NATURALLY-OCCURRING NEUROFIBROMATOSIS IN DAMSELFISH

Damselfish neurofibromatosis [DNF], a neoplastic disease characterized by multiple, neurofibromas and malignant schwannomas, is currently th e only naturally occurring animal model of human neurofibromatosis typ e-1. Previous studies of immune function in DNF affected fish indicate d the potential for significant immunosuppression in advanced stages o f the disease. The current study compares healthy animals with fish ca ptured in the wild bearing spontaneous tumors and with animals bearing experimental tumors transmitted in the laboratory. In order to determ ine the effects of tumor burden on the immune capabilities of these an imals, proliferative responses to mitogens and toward allogeneic cells were tested. The data presented here indicate that animals bearing ad vanced tumors of experimental origins are profoundly immunocompromised . Similarly, some spontaneous tumor-bearing animals are deficient in p roliferative immune responses, and splenocytes from most animals fail to respond to mitogens. However, a proportion of animals with stage 5 spontaneous tumors retain immune reactivity, and are capable of allore actions comparable to those of normal individuals when stimulated with cells from healthy [4/10, 40%] or other tumor-bearing [4/8, 50%] anim als. The contributions of tumor size, distribution and cytokine produc tion to the differential immune impairment are discussed.