The Journal of Experimental Medicine
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Published 19 February 2002. doi:10.1084/jem.20011662
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© Rockefeller University Press, 0022-1007/2002/2/473/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 4, February 18, 2002 473-483

Original Article

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



Robbie B. Mailliard1, Shinichi Egawa1, Quan Cai1, Anna Kalinska1, Svetlana N. Bykovskaya1, Michael T. Lotze1, Martien L. Kapsenberg3, Walter J. Storkus1,2 and Pawel Kalinski1,2

1 Department of Surgery, University of Pittsburgh
2 University of Pittsburgh Cancer Institute, Pittsburgh, PA 15261
3 Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands

Address correspondence to P. Kalinski, Department of Surgery, University of Pittsburgh, W1540 BST, 200 Lothrop St., Pittsburgh, PA 15261. Phone: 412-624-6451; Fax: 412-624-1172; E-mail: KalinskiP{at}msx.upmc.edu

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.

Key Words: T helper subsets • dendritic cells • maturation • IL-12 • CD8+ T cells


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