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Interleukin‐12‐secreting fibroblasts are more efficient than free recombinant interleukin‐12 in inducing the persistent resistance to Mycobacterium avium complex infection
Author(s) -
Bok Yun Kang,
Su Wol Chung,
Yaeji Lim,
E J Kim,
S H Kim,
Seung Yong Hwang,
T S Kim
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00796.x
Subject(s) - biology , cytotoxic t cell , secretion , immunology , immunization , paracrine signalling , microbiology and biotechnology , interleukin , immune system , cytokine , in vitro , endocrinology , receptor , biochemistry
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/10 6 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.