Published online
doi:10.1084/jem.20070176
The Journal of Experimental Medicine, Vol. 204, No. 5, 1095-1106
The Rockefeller University Press, 0022-1007 $30.00
© Soares et al.
A subset of dendritic cells induces CD4+ T cells to produce IFN-
by an IL-12independent but CD70-dependent mechanism in vivo
Helena Soares1,
HaeNa Waechter1,
Nicholas Glaichenhaus3,
Evelyne Mougneau3,
Hideo Yagita4,
Olga Mizenina1,
Diana Dudziak2,
Michel C. Nussenzweig2, and
Ralph M. Steinman1
1 Laboratory of Cellular Physiology and Immunology and Chris Browne Center, and 2 Laboratory of Molecular Immunology and the Howard Hughes Institute, The Rockefeller University, New York, NY 10021
3 E03-44, Institut National de la Sainté et de la Recherche Médicale, University of Nice-Sophia Antipolis, 06560 Valbonne, France
4 Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
CORRESPONDENCE Ralph M. Steinman: steinma{at}mail.rockefeller.edu
Interferon (IFN)-
, a cytokine critical for resistance to infection and tumors, is produced by CD4+ helper T lymphocytes after stimulation by cultured dendritic cells (DCs) that secrete a cofactor, interleukin (IL)-12. We have identified a major IL-12independent pathway whereby DCs induce IFN-
secreting T helper (Th)1 CD4+ T cells in vivo. This pathway requires the membrane-associated tumor necrosis family member CD70 and was identified by targeting the LACK antigen from Leishmania major within an antibody to CD205 (DEC-205), an uptake receptor on a subset of DCs. Another major DC subset, targeted with 33D1 anti-DCIR2 antibody, also induced IFN-
in vivo but required IL-12, not CD70. Isolated CD205+ DCs expressed cell surface CD70 when presenting antigen to T cell receptor transgenic T cells, and this distinction was independent of maturation stimuli. CD70 was also essential for CD205+ DC function in vivo. Detection of the IL-12independent IFN-
pathway was obscured with nontargeted LACK, which was presented by both DC subsets. This in situ analysis points to CD70 as a decision maker for Th1 differentiation by CD205+ DCs, even in Th2-prone BALB/c animals and potentially in vaccine design. The results indicate that two DC subsets have innate propensities to differentially affect the Th1/Th2 balance in vivo and by distinct mechanisms.

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