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The Journal of Immunology, 2004, 172: 4826-4833.
Copyright © 2004 by The American Association of Immunologists

Differential Requirement for the CD40-CD154 Costimulatory Pathway during Th Cell Priming by CD8{alpha}+ and CD8{alpha}− Murine Dendritic Cell Subsets1

Takahiro Yasumi*, Kenji Katamura*, Takakazu Yoshioka*, Taka-aki Meguro*, Ryuta Nishikomori*, Toshio Heike*, Manabu Inobe{dagger}, Shigeyuki Kon{dagger}, Toshimitsu Uede{dagger} and Tatsutoshi Nakahata2,*

* Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan; and {dagger} Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

Dendritic cells (DCs) regulate the development of distinct Th populations and thereby provoke appropriate immune responses to various kinds of Ags. In the present work, we investigated the role CD40-CD154 interactions play during the process of Th cell priming by CD8{alpha}+ and CD8{alpha}− murine DC subsets, which have been reported to differently regulate the Th response. Adoptive transfer of Ag-pulsed CD8{alpha}+ DCs induced a Th1 response and the production of IgG2a Abs, whereas transfer of CD8{alpha}− DCs induced Th2 cells and IgE Abs in vivo. Induction of distinct Th populations by each DC subset was also confirmed in vitro. Although interruption of CD80/CD86-CD28 interactions inhibited Th cell priming by both DC subsets, disruption of CD40-CD154 interactions only inhibited the induction of the Th1 response by CD8{alpha}+ DCs in vivo. CD40-CD154 interactions were not required for the proliferation of Ag-specific naive Th cells stimulated by either DC subset, but were indispensable in the production of IL-12 from CD8{alpha}+ DCs and their induction of Th1 cells in vitro. Taken together, in our immunization model of Ag-pulsed DC transfer, CD40-CD154 interactions play an important role in the development of CD8{alpha}+ DC-driven Th1 responses but not CD8{alpha}− DC-driven Th2 responses to protein Ags.




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