Interleukin-12-secreting fibroblasts are more efficient than free recombinant interleukin-12 in inducing the persistent resistance to Mycobacterium avium complex infection
By. Kang et al., Interleukin-12-secreting fibroblasts are more efficient than free recombinant interleukin-12 in inducing the persistent resistance to Mycobacterium avium complex infection, IMMUNOLOGY, 97(3), 1999, pp. 474-480
To determine whether the paracrine secretion of interleukin-12 (IL-12) can
efficiently stimulate the resistance to Mycobacterium avium complex (MAC) i
nfection, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 U/1
0(6) cells/48 hr) and their effect on MAC infection was investigated in gen
etically 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 ba
cterial load of the lung during the entire 10-week observation period, whil
e rIL-12 reduced the bacterial load initially, at 2 weeks, but not by 10 we
eks 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 ox
ide production by lung cells than did rIL-12 immunization. This work sugges
ts that IL-12-secreting fibroblasts may serve as a vehicle for paracrine se
cretion of IL-12 for immunotherapy of MAC infection.