TY - JOUR
T1 - LAG-3 regulates plasmacytoid dendritic cell homeostasis
AU - Workman, Creg J.
AU - Wang, Yao
AU - El Kasmi, Karim C.
AU - Pardoll, Drew M.
AU - Murray, Peter J.
AU - Drake, Charles G.
AU - Vignali, Dario A.A.
PY - 2009/2/15
Y1 - 2009/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=61449190726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=61449190726&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0800185
DO - 10.4049/jimmunol.0800185
M3 - Article
C2 - 19201841
AN - SCOPUS:61449190726
VL - 182
SP - 1885
EP - 1891
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -