Induction of Th2 cell differentiation in the primary immune response: dendritic cells isolated from adherent cell culture treated with IL-10 prime naive CD4+ T cells to secrete IL-4 |
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Authors: | Liu L; Rich BE; Inobe J; Chen W; Weiner HL |
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Institution: | Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. |
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Abstract: | A number of observations indicate that exposure to IL-4 is essential for
the priming of Th2-type effector T cells and that exposure to IL-12 is
essential for the priming of Th1-type effector T cells. However, the
initial source of IL-4 in the early immune response has not been clearly
identified. Dendritic cells (DC) are the most potent antigen- presenting
cells (APC) in priming naive T cells. In this report, we show that DC
exposed to IL-10 may play an important role in the priming of
IL-4-secreting cells in the early immune response. DC isolated from splenic
adherent cell cultures treated with rIL-10 (IL-10-DC) primed naive
ovalbumin (OVA)-TCR transgenic T cells to secrete IL-4 upon re- stimulation
with OVA and splenic APC. By contrast, DC isolated from rIL- 12, rIL-4 or
control treated cultures induced almost exclusively Th1- type effector T
cells. IL-4 secretion was detected in the primary cultures of IL-10-DC plus
naive CD4+ T cells and the priming of IL-4- secreting T cells by IL-10-DC
was dependent on endogenous IL-4 production in the priming culture since
anti-IL-4 neutralizing antibody completely abrogated the priming of
IL-4-secreting cells. Anti-B7-2 but not anti-B7-1 inhibited the ability of
IL-10-DC to prime T cells to secrete IL-4. Furthermore, the ability of
IL-10 DC to prime for IL-4- secreting T cells was closely related to the
down-regulation of CD40 ligand-mediated IL-12 p70 production by DC in the
primary cultures and was markedly reduced by adding exogenous IL-12 to the
priming cultures. Thus, our findings indicate that early immunologic events
that drive Th2 differentiation involve the effects of IL-10 on DC.
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