Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 45, Pages 17765-17770Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0708767104
Keywords
B7-DC; B7-H1; costimulation; LPS; IL-4
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Funding
- NCI NIH HHS [R01 CA040041, CA40041] Funding Source: Medline
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Despite the importance of programmed death-1 (PD-1) for T cell inhibition, little is known about its intracellular trafficking or requirements for localization to the immunological synapse. Here, we show that in activated T cells, PD-1 is present at the plasma membrane, near the Golgi and in the trans-Golgi network. Unlike CD28 and CTLA-4, PD-1 accumulation at the synapse is extensive only when T cells interact with dendritic cells (DCs) expressing high B7-DC levels. However, B7-H1 is also critically important, especially when the DCs have little B7-DC. Despite this preference, B7-H1(-/-) DCs elicit greater cytokine secretion than B7-DC-/- DCs during T cell restimulation, possibly because they also express less B7-DC. PD-1 and CD28 have similar kinetics of synaptic accumulation, suggesting that the process involves T cell receptor-triggered cytoskeletal reorganization followed by ligand binding.
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