Bovine NK cells can produce gamma interferon in response to the secreted mycobacterial proteins ESAT-6 and MPP14 but not in response to MPB70.
Bovine NK cells have recently been characterized and the present study describes the interaction between NK cells, antigen-presenting cells, and secreted mycobacterial proteins. Gamma interferon (IFN-gamma) production by NK cells was seen in approximately 30% of noninfected calves in response to the Mycobacterium tuberculosis complex-specific protein ESAT-6, MPP14 from Mycobacterium avium subsp. paratuberculosis, and purified protein derivative (PPD) from M. tuberculosis. In contrast, no response was induced by MPB70, which is another M. tuberculosis complex-specific secreted antigen. The production of IFN-gamma by NK cells in whole blood in response to ESAT-6 and MPP14 was demonstrated using intracellular staining together with surface labeling for the NK cell-specific receptor, NKp46, or CD3. Furthermore, the depletion of NK cells from peripheral blood mononuclear cells completely abolished the IFN-gamma production. The response was mediated through stimulation of adherent cells and was largely independent of contact between adherent cells and the NK cells. Neutralization of interleukin-12 only partly inhibited IFN-gamma production, showing that other cytokines were also involved. The demonstration of NK cell-mediated IFN-gamma production in young cattle provides an explanation for the nonspecific IFN-gamma response frequently encountered in young cattle when using the IFN-gamma test in diagnosis of mycobacterial infections.
Olsen
Ingrid
I
National Veterinary Institute, P.O. Box 8156 Dep., 0033 Oslo, Norway. Ingrid.Olsen@vetinst.no
Boysen
Preben
P
Kulberg
Siri
S
Hope
Jayne C
JC
Jungersen
Gregers
G
Storset
Anne K
AK
D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C060216:MPB70 protein, Mycobacterium bovis; D007371:Interferon-gamma