PRODUCTION OF GAMMA-INTERFERON BY NATURAL-KILLER-CELLS FROM TAXOPLASMA GONDII-INFECTED SCID MICE - REGULATION BY INTERLEUKIN-10, INTERLEUKIN-12, AND TUMOR-NECROSIS-FACTOR-ALPHA
Ca. Hunter et al., PRODUCTION OF GAMMA-INTERFERON BY NATURAL-KILLER-CELLS FROM TAXOPLASMA GONDII-INFECTED SCID MICE - REGULATION BY INTERLEUKIN-10, INTERLEUKIN-12, AND TUMOR-NECROSIS-FACTOR-ALPHA, Infection and immunity, 62(7), 1994, pp. 2818-2824
Previous studies of mice have implicated natural killer (NK) cells as
mediators of protective activity against Toxoplasma gondii through the
ir production of gamma interferon (IFN-gamma). In the present study, w
e have compared NK-cell activity in infected and uninfected SCID mice.
Our data reveal that infection results in increased levels of IFN-gam
ma in serum and elevated NK-cell activity but that these NK cells were
not cytotoxic for T. gondii-infected p815 cells. Treatment with anti-
IFN-gamma antibody abrogated the increase in NK-cell activity and resu
lted in earlier mortality of infected mice. In vivo treatment with ant
i-asialo GM1 antiserum reduced NK cell activity and levels of IFN-gamm
a in serum but did not alter time to death. Spleen cells from infected
mice produced higher levels of IFN-gamma than those from uninfected m
ice when stimulated in vitro with live T. gondii or parasite antigen p
reparations. Further analysis revealed that interleukin 10 (IL-10) inh
ibited, whereas tumor necrosis factor alpha (TNF-alpha) and 1L-12 enha
nced, IFN-gamma production by spleen cells from infected or uninfected
mice. The combination of IL-12 and TNF-alpha induced higher levels of
IFN-gamma from whole spleen cells of infected mice than from those of
uninfected mice. Depletion of the adherent cell population from the s
pleen cells of infected mice led to a significant reduction in the lev
els of IFN-gamma produced after stimulation with IL-12 plus TNF-alpha.
Similar results did not occur with cells from uninfected mice. These
data indicate that other cytokines produced by the adherent fell popul
ation from infected mice may be involved in maximal production of IFN-
gamma by NK cells stimulated with IL-12 and TNF-alpha. To assess the i
mportance of endogenous IL-12, a polyclonal anti-IL-12 was administere
d to infected SCID mice. This treatment led to earlier mortality, indi
cating that endogenous IL-12 mediates resistance to T. gondii.