K. Abdi et Sh. Herrmann, CTL GENERATION IN THE PRESENCE OF IL-4 IS INHIBITED BY FREE P40 - EVIDENCE FOR EARLY AND LATE IL-12 FUNCTION, The Journal of immunology, 159(7), 1997, pp. 3148-3155
The cytokine requirements for the generation of a CTL response were ex
amined using thymocyte responders stimulated with Con A, In agreement
with previous reports, IL-4 alone can generate a strong CTL response,
To determine whether IL-12 was required for this response, we added ei
ther a neutralizing Ab against IL-12 or an antagonist of IL-12 functio
n, p40, Both anti-IL-12 and p40 were found to inhibit the generation o
f CTL in the presence of IL-4, Consistent with these data, exogenous I
L-12 was found to synergize with IL-4, particularly, when IL-4 was add
ed at levels unable to generate a CTL response alone. This synergistic
response was observed whether IL-12 was added at the beginning of cul
ture along with IL-4 or after the first day to cultures initiated with
IL-4, Likewise, the combination of IL-2 plus IL-12 evoked a strong sy
nergistic response when cultures were initiated with IL-2 and IL-12 wa
s added initially or after the first day of culture. Addition of eithe
r IL-2 or IL-12 alone did not generate a response. In contrast to thes
e data showing that IL-12 was able to signal late in culture, p40 inhi
bited CTL generation in response to IL-4 only when added at the beginn
ing of culture, These results imply that CTL induction involves a cruc
ial early IL-12 signal, which once delivered permits cells to respond
to a later IL-12 signal, These data are consistent with the idea that
free circulating p40 could inhibit the generation of CTL by antagonizi
ng the Early IL-12 ''differentiatian'' signal.