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Laboratoire d’Immunochimie, Commissariat à l’Energie Atomique-Grenoble/Département Réponse et Dynamique Cellilaires, Institut National de la Santé et de la Recherche Médicale Unité 548, Université Joseph Fourier, Grenoble, France
IL-12 is mainly produced by CD8
+ dendritic cells
(DCs) and induces Th1 polarization of the immune response. We
investigated the influence of lymphocytes on splenic DC (SDC) and
thymic DC (TDC) development and on their IL-12 production capacity.
First, CD3
-/- mice, lacking T cells, and
RAG-2-/- mice, lacking T and B cells, possess numbers of
SDCs, TDCs, and CD8+ SDCs similar to wild-type (WT)
mice. Second, SDCs and TDCs from CD3-/- mice do not
secrete IL-12 in vitro after different stimulations, whereas DCs from
pT-/- mice, possessing reduced T cell number, and
RAG-2-/- mice, produce an IL-12 level similar to that of
WT DCs. We show that T lymphocytes restore the capacity of DCs to
produce IL-12 after stimulation in vivo by reconstitution of
CD3-/- mice with WT T cells and in vitro by coculture
of CD3-/- DCs with WT T cells. The regulation of IL-12
production occurred at the transcriptional level, with an increase of
IL-12p35 transcripts and a decrease of IL-12p40 transcripts. Although
IL-4 restores IL-12 production by CD3-/- SDCs,
anti-IL-4 Abs inhibited only partially the IL-12 production in
coculture of CD3-/- DCs and WT T cells. Taken
together, these data show that T lymphocytes potentiate IL-12
production by DCs and that IL-4 is not solely involved in this
regulation. In conclusion, B and T cells exert balanced actions on DCs
by respectively inhibiting or promoting IL-12
production.
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