Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation
Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 3, 1491-1496, February 5, 2002
Giovanna Angelini*,, Stefania Gardella*, Massimo Ardy*, Maria Rosa Ciriolo, Giuseppe Filomeni, Giovanna Di Trapani§, Frank Clarke§, Roberto Sitia¶, and Anna Rubartelli*
* Protein Biology Unit, National Cancer Research Institute, 16132 Genoa, Italy; Department of Biomedical Sciences, University of Chieti, 66100 Chieti, Italy; § School of Biomolecular and Biomedical Science, Griffith University, Brisbane 4111, Australia; and ¶ Università Vita-Salute San Raffaele, 20132 Milan, Italy
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 , 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.
------------------------------------------------------------
www.pnas.org/cgi/doi/10.1073/pnas.022630299 |
