Dendritic cells control T cell tonic signaling required for responsiveness to foreign antigen.
Dendritic cells (DCs) are key components of the adaptive immune system contributing to initiation and regulation of T cell responses. T cells continuously scan DCs in lymphoid organs for the presence of foreign antigen. However, little is known about the functional consequences of these frequent T cell-DC interactions without cognate antigen. Here we demonstrate that these contacts in the absence of foreign antigen serve an important function, namely, induction of a basal activation level in T cells required for responsiveness to subsequent encounters with foreign antigens. This basal activation is provided by self-recognition of MHC molecules on DCs. Following DC depletion in mice, T cells became impaired in TCR signaling and immune synapse formation, and consequently were hyporesponsive to antigen. This process was reversible, as T cells quickly recovered when the number of DCs returned to a normal level. The extent of T cell reactivity correlated with the degree of DC depletion in lymphoid organs, suggesting that a full DC compartment guarantees optimal T cell responsiveness. These findings indicate that DCs are specialized cells that not only present foreign antigen, but also promote a "tonic" state in T cells for antigen responsiveness.
Division of Molecular Immunology, German Cancer Research Center, 69120 Heidelberg, Germany.
Kristin
K
Hochweller
Guido H
GH
Wabnitz
Yvonne
Y
Samstag
Janine
J
Suffner
Günter J
GJ
Hämmerling
Natalio
N
Garbi
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D002470:Cell Survival / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D054992:Immunological Synapses / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018183:Transplantation Chimera / Q000276:immunology
C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins