Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 13, Pages 5931-5936Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911877107
Keywords
antigen sensitivity; diphtheria toxin receptor; T cell reactivity
Categories
Funding
- EU [LSHG-CT-2005-005203]
- Cancer Immunotherapy [LSH-2004-2.2.0-5]
- Helmholtz Alliance for Immunotherapy
- German Ministry of Education and Research [NGFN-2 01GS0452]
- German Research Foundation [SB405, Sa393/3-3, SFB405/A4]
- Tumorzentrum Heidelberg-Mannheim [D.100.27.963]
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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.
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