RELATIVE ROLES OF T-CELLS AND MACROPHAGES IN CYTOKINE-MEDIATED FUNCTIONAL TRANSFORMATION OF CULTURED SPLENIC DENDRITIC CELLS

Splenic dendritic cells resemble epidermal Langerhans cells in the sense that when both cell types are placed in culture for 1 or more days they undergo a functional transformation that equips them to activate unprimed syngeneic T cells. Among Langerhans cells, this transformation has been ascribed to contaminating keratinocytes that are present in cell suspensions prepared from epidermis. Cytokines released from cultured keratinocytes, particularly GM-CSF and IL-1, have been implicated in mediating the functional transformation observed among cultured Langerhans cells. The present experiments have examined the nature of the cytokines responsible for functional conversion of fresh to cultured dendritic cells harvested from spleens of normal mice and have attempted to identify among the cultured cells the cellular source(s) of these factors. The results indicate that splenic dendritic cells acquire unique accessory properties for activation of naive T cells when placed in vitro because factors generated within the culture, especially GM-CSF and IL-1 beta, are present. Our evidence shows that splenic T cells and phagocytic cells, presumably macrophages, contribute to the presence of these conversion-promoting factors. Thus, this evidence suggests that splenic dendritic cells within the spleen of normal mice, like Langerhans cells within the epidermis of normal, unperturbed skin, exist in vivo in a proactive state with respect to the capacity to induce priming among naive T cells. Acquisition of unique accessory cell function depends upon other cell types within spleen, such as T cells and macrophages that secrete GM-CSF and IL-1 beta. These cytokines, as well as other undefined factors, enable dendritic cells to acquire the accessory properties required to activate resting T cells. (C) 1995 Academic Press, Inc.