S. Marx et al., ACTIVATION OF HUMAN GAMMA-DELTA T-CELLS BY MYCOBACTERIUM-TUBERCULOSISAND DAUDI LYMPHOMA-CELLS - DIFFERENTIAL REGULATORY EFFECT OF IL-10 AND IL-12, The Journal of immunology, 158(6), 1997, pp. 2842-2848
Peripheral blood V gamma 9/V delta 2 T cells proliferate vigorously in
response to heat-killed Mycobacterium tuberculosis (Mtb) and Daudi Bu
rkitt's lymphoma cells. We have analyzed the respective roles of IL-10
and IL-12 in gamma delta T cell activation, using the selective expan
sion of V gamma 9 cells in Mtb- or Daudi-stimulated PBMC as a readout.
IL-10 inhibited in a dose-dependent fashion the V gamma 9 responsiven
ess to Mtb. In contrast, IL-10 did not impair reactivity toward Daudi
cells, even when added at 10 ng/ml. The inhibitory action of IL-10 cou
ld be overcome by the exogenous supply of IL-2 or IL-12. Blockade of e
ndogenous IL-10 by neutralizing mAb increased responsiveness to Mtb bu
t not to Daudi cells. Low concentrations of exogenous IL-12 increased
the V gamma 9 responsiveness to Mtb in 6 of 11 healthy donors. In cont
rast, IL-12 inhibited V gamma 9 cell expansion in response to Daudi st
imulation in all of the tested individuals. Neutralizing anti-IL-12 Ab
significantly suppressed V gamma 9 responsiveness to Mtb in IL-12 non
responders but only slightly inhibited the latter responsiveness in IL
-12 responders. The effect of anti-IL-12 Ab correlated with the level
of Mtb-stimulated endogenous IL-12 production. In purified gamma delta
T cells, IL-12 synergized with IL-2 to stimulate cellular expansion i
n response to Daudi cells. This effect was reduced when T cell-deplete
d APC were added back. Finally, neutralization of endogenous IFN-gamma
by Ab abrogated V gamma 9 cell responsiveness to Mtb but exerted only
a minor inhibition of the reactivity toward Daudi cells. Taken togeth
er, these results reveal significant differences in the cytokine requi
rement of gamma delta T cell activation by Mtb or Daudi lymphoma cells
, respectively.