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Institute for Immunology, Johannes Gutenberg University, Mainz, Germany
IL-4 was found to be the essential differentiation factor for Th2
cells and simultaneously to be a potent inhibitor of Th1 development
that is induced by IFN-
and IL-12. Furthermore, it was demonstrated
that TGF-ß can also inhibit Th1 development. In this work, we
demonstrate that polyclonal activation of
Mel-14highCD4+ T cells by immobilized
anti-
ßTCR mAb together with a mixture of IL-4 and TGF-ß can
lead to the development of both Th1 and Th2 cells, depending on the
concentration of these cytokines. Additional experiments revealed that
Th1 induction by a combination of IL-4 and TGF-ß depends on the
presence of endogenous IFN-, and that this alternative Th1
development is further enhanced by IL-12, but is not dependent on this
cytokine. Moreover, naive OVA323–339-specific Th cells
that were stimulated by APCs and OVA323–339 peptide
differentiated toward Th1 cells after priming in the presence of IL-4
in combination with TGF-ß. Hence, this finding confirmed the results
obtained by polyclonal activation of naive CD4+ Th cells
and implicates that this alternative Th1 development may also occur in
vivo under the influence of TGF-ß and IL-4 independently of the
Th1-promoting effect of IL-12.
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