Complementary dendritic cell-activating function of CD8 + and CD4 + T cells: Helper role of CD8 + T cells in the development of T helper type responses

Robbie B. Mailliard, Shinichi Egawa, Quan Cai, Anna Kalinska, Svetlana N. Bykovskaya, Michael T. Lotze, Martien L. Kapsenberg, Walter J. Storkus, Pawel Kalinski

Research output: Contribution to journalArticlepeer-review

129 Citations (Scopus)

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-γ 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-α- and IFN-γ-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.

Original languageEnglish
Pages (from-to)473-483
Number of pages11
JournalJournal of Experimental Medicine
Volume195
Issue number4
DOIs
Publication statusPublished - 2002 Feb 18
Externally publishedYes

Keywords

  • CD8 T cells
  • Dendritic cells
  • IL-12
  • Maturation
  • T helper subsets

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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