PMID- 11854360 OWN - NLM STAT- MEDLINE DCOM- 20020321 LR - 20190508 IS - 0022-1007 (Print) IS - 1540-9538 (Electronic) IS - 0022-1007 (Linking) VI - 195 IP - 4 DP - 2002 Feb 18 TI - Complementary dendritic cell-activating function of CD8+ and CD4+ T cells: helper role of CD8+ T cells in the development of T helper type 1 responses. PG - 473-83 AB - Dendritic cells (DCs) activated by CD40L-expressing CD4+ T cells act as mediators of "T helper (Th)" signals for CD8+ T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4+ T cells, is supported by the complementary DC-activating signals from both CD4+ and CD8+ T cells. Cord blood- or peripheral blood-isolated naive CD8+ T cells do not express CD40L, but, in contrast to naive CD4+ T cells, they are efficient producers of IFN-gamma at the earliest stages of the interaction with DCs. Naive CD8+ T cells cooperate with CD40L-expressing naive CD4+ T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4+ T cell responses. Moreover, the recognition of major histocompatibility complex class I-presented epitopes by antigen-specific CD8+ T cells results in the TNF-alpha- and IFN-gamma-dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I-restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I-presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections. FAU - Mailliard, Robbie B AU - Mailliard RB AD - Department of Surgery, Cancer Institute, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15261, USA. FAU - Egawa, Shinichi AU - Egawa S FAU - Cai, Quan AU - Cai Q FAU - Kalinska, Anna AU - Kalinska A FAU - Bykovskaya, Svetlana N AU - Bykovskaya SN FAU - Lotze, Michael T AU - Lotze MT FAU - Kapsenberg, Martien L AU - Kapsenberg ML FAU - Storkus, Walter J AU - Storkus WJ FAU - Kalinski, Pawel AU - Kalinski P LA - eng GR - R01 CA057840/CA/NCI NIH HHS/United States GR - 1P01 CA 74343/CA/NCI NIH HHS/United States GR - 1R01 CA 57840/CA/NCI NIH HHS/United States GR - 1R01 CA 82016/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Tumor Necrosis Factor-alpha) RN - 147205-72-9 (CD40 Ligand) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - CD40 Ligand/biosynthesis/immunology MH - CD8-Positive T-Lymphocytes/*immunology/metabolism MH - Cell Differentiation MH - Cell Line MH - Dendritic Cells/cytology/*immunology/metabolism MH - Flow Cytometry MH - Histocompatibility Antigens Class I/immunology MH - Humans MH - Influenza, Human/immunology MH - Interferon-gamma/biosynthesis/pharmacology MH - Interleukin-12/biosynthesis/immunology MH - Melanoma/immunology MH - Th1 Cells/*immunology/metabolism MH - Tumor Necrosis Factor-alpha/biosynthesis/immunology PMC - PMC2193623 EDAT- 2002/02/21 10:00 MHDA- 2002/03/22 10:01 PMCR- 2002/08/18 CRDT- 2002/02/21 10:00 PHST- 2002/02/21 10:00 [pubmed] PHST- 2002/03/22 10:01 [medline] PHST- 2002/02/21 10:00 [entrez] PHST- 2002/08/18 00:00 [pmc-release] AID - 011662 [pii] AID - 10.1084/jem.20011662 [doi] PST - ppublish SO - J Exp Med. 2002 Feb 18;195(4):473-83. doi: 10.1084/jem.20011662.