Accessory cell dependent T lymphocyte proliferation: potent activity of dendritic cells.

The proliferative response of T lymphocytes to Concanavalin A (Con A) and the oxidative mitogens, sodium periodate (NaIO4) and neuraminidase plus galactose oxidase (NGO), requires the participation of dendritic cells (DC). High density cells (HDC) recovered from the fractionation of lymph node cells on a discontinuous gradient of bovine plasma albumin did not respond to NaIO4, but responded well above background levels to NGO or Con A. Addition of DC elevated these responses further. By an indirect panning technique, the HDC were exhaustively depleted of cells expressing Ia surface antigens. Ninety-nine percent of these HDC displayed T cell surface antigens. These Ia- T cells did not respond to any of the three mitogen treatments until DC were added, whereupon the proliferative responses were restored in a concentration-dependent manner, with maximal levels attained at a DC to T cell ratio of 1:200. The addition of a purified preparation of IL2 to untreated or mitogen-treated Ia- T cells increased the proliferative responses slightly and was unable to substitute for the potent activity of dendritic cells. Only the addition of DC was able to stimulate mitogen-induced proliferation to maximal levels. The limiting factor in these responses was the number of dendritic cells, which controlled the induction of both the release of IL2 and responsiveness to IL2 for the oxidative mitogens and Con A. Thus, DC function as potent accessory cells for each of the three mitogens.