Induction of in vivo persistent anti-mycobacterial activity by interferon-gamma-secreting fibroblasts

To determine whether the paracrine secretion of interferon-gamma (TFN-gamma ) can efficiently stimulate the resistance to Mycobacterium avium complex ( MAC) infection, 3T3 fibroblasts were stably transduced to secrete IFN-gamma (500 units/10(6) cells/48 h) and their effects an MAC infection were inves tigated in genetically susceptible BALB/c mice, compared with that of free recombinant IFN-gamma (rIFN-gamma), Immunization with IFN-gamma-secreting f ibroblasts (3T3-IFN-gamma) during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while rIFN-gamma reduced the bacterial load at initial 1 week but not by 8 weeks postinfection. Furthermore, immunization with the 3T3-IFN-gamma cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than those of rIFN-gamma immunization. This work suggest that IFN-gamma-secreting fibrobl asts may serve as a vehicle for paracrine secretion of IFN-gamma in immunot herapy of MAC infection. (C) 2000 Elsevier Science Ltd. All rights reserved .