Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation

Giovanna Angelini, Stefania Gardella, Massimo Ardy, Maria Rosa Ciriolo, Giuseppe Filomeni, Giovanna Di Trapani, Frank Clarke, Roberto Sitia, Anna Rubartelli

Research output: Contribution to journalArticle

Abstract

T lymphocytes are defective in cystine uptake and thus require exogenous thiols for activation and function. Here we show that monocyte-derived human dendritic cells (DCs) release cysteine in the extracellular space. Cysteine generation is increased by lipopolysaccharide and tumor necrosis factor α, and by contact with T cells specifically recognizing soluble or alloantigens. These stimuli also induce thioredoxin (TRX) accumulation in DCs. However, only the contact with antigen-specific T cells triggers TRX secretion by the antigen-presenting cells. Fewer extracellular thiols are recovered after DC-T cell interactions when cystine uptake or TRX activity are inhibited. In addition, glutamate (Glu) and anti-TRX-inactivating antibodies inhibit antigen-dependent T lymphocyte proliferation. These findings indicate that, during antigen presentation, DCs uptake cystine and release cysteine and TRX, thus providing a reducing microenvironment that facilitates immune response.

Original languageEnglish
Pages (from-to)1491-1496
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number3
DOIs
Publication statusPublished - Feb 5 2002

ASJC Scopus subject areas

  • Genetics
  • General

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