title: 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.
abstract: 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.
authors.affiliation: Department of Surgery, Cancer Institute, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
authors.forename: Robbie B
authors.initials: RB
authors.lastname: Mailliard
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Quan
authors.initials: Q
authors.lastname: Cai
authors.forename: Anna
authors.initials: A
authors.lastname: Kalinska
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Bykovskaya
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
mesh_terms: D023201:CD40 Ligand / Q000096:biosynthesis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007251:Influenza, Human / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma