LAG-3 regulates plasmacytoid dendritic cell homeostasis

Creg J. Workman, Yao Wang, Karim C. El Kasmi, Drew M. Pardoll, Peter J. Murray, Charles G. Drake, Dario A.A. Vignali

Research output: Contribution to journalArticlepeer-review

Abstract

Lymphocyte activation gene 3 (LAG-3) is a CD4-related, activation-induced cell surface molecule expressed by various lymphoid cell types and binds to MHC class II with high affinity. We have previously shown that LAG-3 negatively regulates the expansion of activated T cells and T cell homeostasis, and is required for maximal regulatory T cell function. In this study, we demonstrate for the first time that LAG-3 is also expressed on CD11clow/B220 +/PDCA-1+ plasmacytoid dendritic cells (pDCs). Lag3 expression, as determined by real time PCR, was ∼10-fold greater in pDCs than in either regulatory T cells or activated T effector cells. Activated pDCs also generate ∼5 times more sLAG-3 than activated T cells. LAG-3-deficient pDCs proliferate and expand more than wild-type pDCs in vivo in response to the TLR9 ligand, CpG. However, the effect of LAG-3 appears to be selective as there was no effect of LAG-3 on the expression of MHC class II, TLR9, and chemokine receptors, or on cytokine production. Lastly, adoptive transfer of either Lag3+/+ or Lag3-/- T cells plus or minus Lag3 +/+ or Lag3-/- pDCs defined a role for LAG-3 in controlling pDC homeostasis as well as highlighting the consequences of deregulated Lag3-/- pDCs on T cell homeostasis. This raised the possibility of homeostatic reciprocity between T cells and pDCs. Collectively, our data suggests that LAG-3 plays an important but selective cell intrinsic and cell extrinsic role in pDC biology, and may serve as a key functional marker for their study.

Original languageEnglish (US)
Pages (from-to)1885-1891
Number of pages7
JournalJournal of Immunology
Volume182
Issue number4
DOIs
StatePublished - Feb 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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