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.
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 CD8alpha+ 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.
Krug
Anne
A
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63108, USA. mcella@pathology.wustl.edu
Veeraswamy
Ravi
R
Pekosz
Andrew
A
Kanagawa
Osami
O
Unanue
Emil R
ER
Colonna
Marco
M
Cella
Marina
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D002454:Cell Differentiation; D016764:Cell Polarity; D003713:Dendritic Cells / Q000502:physiology; D007370:Interferon Type I / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis; D007962:Leukocytes / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology*
D007370:Interferon Type I; D007376:Interleukin-2; D018664:Interleukin-12