The Journal of Experimental Medicine
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Published online 31 March 2003 doi:10.1084/jem.20021091
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© Rockefeller University Press, 0022-1007/2003/4/899 $5.00
The Journal of Experimental Medicine, Volume 197, Number 7, 899-906

Interferon-producing Cells Fail to Induce Proliferation of Naive T Cells but Can Promote Expansion and T Helper 1 Differentiation of Antigen-experienced Unpolarized T Cells

Anne Krug1, Ravi Veeraswamy1, Andrew Pekosz2, Osami Kanagawa1, Emil R. Unanue1, Marco Colonna1 and Marina Cella1

1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
2 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110

Address correspondence to Marina Cella, Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63108. Phone: 314-362-0367; Fax: 314-362-4096; E-mail: mcella{at}pathology.wustl.edu

Interferon-producing cells (IPCs) secrete high levels of type I interferon in response to certain viruses. The lack of lineage markers, the expression of major histocompatibility complex (MHC) class II and the capacity to stimulate allogeneic T cells have led these cells to be classified as a subset of dendritic cells (DCs), called plasmacytoid DCs (PDCs). However, the role of IPCs/PDCs in initiating primary immune responses remains elusive. Here we examined the antigen presenting capacity of murine IPCs in antigen specific systems. While CD8{alpha}+ and CD11b+ DCs induced logarithmic expansion of naive CD4 and CD8 T cells, without conferring T helper commitment at a first encounter, primary IPCs lacked the ability to stimulate naive T cells. However, when antigen-experienced, nonpolarized T cells expanded by classical DC subsets, were restimulated by IPCs, they proliferated and produced high amounts of IFN-{gamma}. These data indicate that IPCs can effectively stimulate preactivated or memory-type T cells and exert an immune-regulatory role. They also suggest that expansion of naive T cells and acquisition of effector function during antigen-specific T cell responses may involve different antigen-presenting cell (APC) types. Independent and coordinated control of T cell proliferation and differentiation would provide the immune system with greater flexibility in regulating immune responses.

Key Words: interferon-producing cells • dendritic cells • Th1 cells • unpolarized T cells


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