PMID- 15067060 OWN - NLM STAT- MEDLINE DCOM- 20040727 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 172 IP - 8 DP - 2004 Apr 15 TI - Differential requirement for the CD40-CD154 costimulatory pathway during Th cell priming by CD8 alpha+ and CD8 alpha- murine dendritic cell subsets. PG - 4826-33 AB - 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. FAU - Yasumi, Takahiro AU - Yasumi T AD - Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Katamura, Kenji AU - Katamura K FAU - Yoshioka, Takakazu AU - Yoshioka T FAU - Meguro, Taka-aki AU - Meguro TA FAU - Nishikomori, Ryuta AU - Nishikomori R FAU - Heike, Toshio AU - Heike T FAU - Inobe, Manabu AU - Inobe M FAU - Kon, Shigeyuki AU - Kon S FAU - Uede, Toshimitsu AU - Uede T FAU - Nakahata, Tatsutoshi AU - Nakahata T LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (CD40 Antigens) RN - 0 (CD8 Antigens) RN - 0 (CD8alpha antigen) RN - 0 (Cytokines) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Animals MH - CD40 Antigens/biosynthesis/metabolism/*physiology MH - CD40 Ligand/biosynthesis/metabolism/*physiology MH - CD8 Antigens/*biosynthesis/metabolism MH - Cell Division/immunology MH - Cells, Cultured MH - Cytokines MH - Dendritic Cells/*immunology/*metabolism/transplantation MH - Immunophenotyping MH - Lymphocyte Activation/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Signal Transduction/*immunology MH - T-Lymphocytes, Helper-Inducer/cytology/*immunology/metabolism MH - Th1 Cells/immunology EDAT- 2004/04/07 05:00 MHDA- 2004/07/28 05:00 CRDT- 2004/04/07 05:00 PHST- 2004/04/07 05:00 [pubmed] PHST- 2004/07/28 05:00 [medline] PHST- 2004/04/07 05:00 [entrez] AID - 10.4049/jimmunol.172.8.4826 [doi] PST - ppublish SO - J Immunol. 2004 Apr 15;172(8):4826-33. doi: 10.4049/jimmunol.172.8.4826.