Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

Jacques Banchereau, Sandra Zurawsk, Lu Ann Thompson-Snipes, Jean Philippe Blanck, Sandra Clayton, Adiel Munk, Yanying Cao, Zhiqing Wang, Sunaina Khandelwal, Jiancheng Hu, William H. McCoy IV, Karolina A. Palucka, Yoram Reiter, Daved H. Fremont, Gerard Zurawski, Marco Colonna, Andrey S. Shaw, Eynav Klechevsky

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Human Langerhans cells (LCs) are highly efficient at priming cytolytic CD8+ T cells compared with dermal CD14+ dendritic cells (DCs). Here we show that dermal CD14+ DCs instead prime a fraction of naïve CD8+ T cells into cells sharing the properties of type 2 cytokine-secreting CD8+ T cells (TC2). Differential expression of the CD8-antagonist receptors on dermal CD14+ DCs, the Ig-like transcript (ILT) inhibitory receptors, explains the difference between the two types of DCs. Inhibition of CD8 function on LCs inhibited cytotoxic T lymphocytes (CTLs) and enhanced TC2 generation. In addition, blocking ILT2 or ILT4 on dermal CD14+ DCs enhanced the generation of CTLs and inhibited TC2 cytokine production. Lastly, addition of soluble ILT2 and ILT4 receptors inhibited CTL priming by LCs. Thus, ILT receptor expression explains the polarization of CD8+ T-cell responses by LCs vs. dermal CD14+ DCs.

Original languageEnglish
Pages (from-to)18885-18890
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number46
DOIs
StatePublished - Nov 13 2012

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