T-HELPER TYPE-1 DEVELOPMENT OF NAIVE CD4(-CELLS REQUIRES THE COORDINATE ACTION OF INTERLEUKIN-12 AND INTERFERON-GAMMA AND IS INHIBITED BY TRANSFORMING GROWTH-FACTOR-BETA() T)
E. Schmitt et al., T-HELPER TYPE-1 DEVELOPMENT OF NAIVE CD4(-CELLS REQUIRES THE COORDINATE ACTION OF INTERLEUKIN-12 AND INTERFERON-GAMMA AND IS INHIBITED BY TRANSFORMING GROWTH-FACTOR-BETA() T), European Journal of Immunology, 24(4), 1994, pp. 793-798
It was observed in vitro and in vivo that both interferon (IFN)-gamma
and interleukin (IL)-12 can promote the development of T helper type 1
(T(H)1) cells. Since IL-12 was shown to be a costimulator for the pro
duction of IFN-gamma by Tor natural killer (NK) cells, IL-12 might pla
y only an indirect role in T(H)1 differentiation by providing IFN-gamm
a which represents the essential differentiation factor. Using anti-CD
3 monoclonal antibody (mAb) for activation of naive CD4(+) T cells in
the absence of accessory cells we could demonstrate that costimulation
by IFN-gamma alone results only in marginal T(H)1 development. Simila
rly, IL-12 in the absence of IFN-gamma is only a poor costimulator for
inducing differentiation towards the T(H)1 phenotype. Our data indica
te that both cytokines are required to allow optimal T(H)1 development
and that IL-12 has a dual role, it promotes differentiation by direct
costimulation of the T cells and also enhances the production of IFN-
gamma which serves as a second costimulator by an autocrine mechanism.
Another cytokine that was reported to favor T(H)1 differentiation in
certain experimental systems is transforming growth factor (TGF)-beta.
With naive CD4(+) T cells employed in this study TGF-beta strongly in
hibited the production of IFN-gamma triggered by IL-12 as well as the
IL-12-induced T(H)1 development. When TGF-beta was combined with anti-
IFN-gamma mAb for neutralization of endogenous IFN-gamma the T(H)1-ind
ucing capacity of IL-12 was completely suppressed.