Anti-CD3 single-chain Fv/interleukin-18 fusion DNA induces anti-mycobacterial resistance via efficient interferon-gamma production in BALB/c mice infected with Mycobacterium avium.
T helper type 1 (Th1) cell-mediated immune response performs a critical role in the induction of host defenses against a variety of intracellular pathogens. We recently demonstrated that the linkage between interleukin (IL)-18 and anti-CD3sFv genes confined the effect of IL-18 to the CD3+ T cells, resulting in the efficient induction of Thl immune responses. In this study, we attempted to determine whether the anti-CD3 single-chain Fv/IL-18 fusion DNA (pAnti-CD3sFv/IL-18) could stimulate resistance to Mycobacterium avium infection in genetically susceptible BALB/c mice. Immunization with pAnti-CD3sFv/IL-18 DNA during intranasal infection with M. avium resulted in a significant reduction in the bacterial load in the lung throughout the entire 10-week observation period. Immunization with pAnti-CD3sFv/IL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by the lung cells, as compared with the injection of pAnti-CD3sFv DNA, or of a simple mixture of pAnti-CD3sFv DNA and pIL-18 DNA. Furthermore, the lung cells of the mice injected with pAnti-CD3sFv/IL-18 DNA exhibited persistent production of IFN-gamma. Treatment with anti-IFN-gamma antibody resulted in an abrogation of anti-mycobacterial effects in mice injected with pAnti-CD3sFv/IL-18 DNA. These results indicate that vaccination with the pAnti-CD3sFv/IL-18 fusion DNA induces significant resistance to M. avium infection, via the production of IFN-gamma in CD4+ T cells.
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Seung H
SH
Kim
Daeho
D
Cho
Tae S
TS
Kim
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*; D009569:Nitric Oxide / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D017252:CD3 Complex; D007135:Immunoglobulin Variable Region; D020382:Interleukin-18; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D009569:Nitric Oxide; D007371:Interferon-gamma