Induction of in vivo persistent anti-mycobacterial activity by interferon-gamma-secreting fibroblasts.
To determine whether the paracrine secretion of interferon-gamma (IFN-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 on MAC infection were investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IFN-gamma (rIFN-gamma). Immunization with IFN-gamma-secreting fibroblasts (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 fibroblasts may serve as a vehicle for paracrine secretion of IFN-gamma in immunotherapy of MAC infection.
Kim
T S
TS
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, South Korea. taekim@chonnam.chonnam.ac.kr
Chung
S W
SW
Kang
B Y
BY
Choe
Y Y
YY
Hwang
S Y
SY
D016475:3T3 Cells; D000818:Animals; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D011994:Recombinant Proteins; D014162:Transfection; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma