Interleukin-12-secreting fibroblasts are more efficient than free recombinant interleukin-12 in inducing the persistent resistance to Mycobacterium avium complex infection

To determine whether the paracrine secretion of interleukin-12 (IL-12) can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 U/10⁶ cells/48 hr) and their effect on MAC infection was investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-12 (rIL-12). Injection with IL-12-secreting fibroblasts (3T3-IL-12) during intranasal infection with MAC resulted in a significant decrease in the bacterial load of the lung during the entire 10-week observation period, while rIL-12 reduced the bacterial load initially, at 2 weeks, but not by 10 weeks postinfection. Lung CD4⁺ T cells in mice injected with the 3T3-IL-12 cells showed a persistent T helper type 1 (Th1) response throughout the 10- week period. Furthermore, immunization with the 3T3-IL-12 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than did rIL-12 immunization. This work suggests that IL-12-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-12 for immunotherapy of MAC infection.