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Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
IL-4 is known to promote the differentiation of CD4+ T
cells into IL-4-secreting Th2 cells. However, the cellular source of
the early burst of IL-4 that drives Th2 responses in vivo has not been
conclusively identified. Mice deficient for the IL-4 receptor
-chain
(IL-4R
-/-) retain the capacity to secrete IL-4 and can
be used to identify those cell types that produce IL-4 without a
requirement for prior IL-4-mediated stimulation. To address whether
naive, conventional CD4+ T cells may act as initial
producers of IL-4 in Ag-specific responses, we crossed the BALB/c
IL-4R
-/-mice to DO11.10/scid TCR
transgenic mice. Lymph node cells from wild-type and
IL-4R
-/- DO11.10/scid mice secreted
50 pg of IL-4 per106 cells within 48 h after
peptide stimulation. This small amount of IL-4 was sufficient to cause
the differentiation of wild-type CD4+ T cells into Th2
cells, particularly if IFN-
and IL-12 were neutralized during the
priming cultures. CD4+ cells from the
IL-4R
-/- mice gave rise to a minor proportion (
2%)
of IL-4-producing cells upon stimulation in the presence of
anti-IFN-
and anti-IL-12. These data show that conventional,
naive CD4+ T cells may be considered as initial sources of
IL-4 and, in the absence of IFN-
and IL-12, this IL-4 can induce Th2
polarization.
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