TY - JOUR
T1 - BST2/Tetherin is constitutively expressed on human thymocytes with the phenotype and function of Treg cells
AU - Epeldegui, Marta
AU - Blom, Bianca
AU - Uittenbogaart, Christel H.
PY - 2015
Y1 - 2015
N2 - In contrast to peripheral plasmacytoid DCs (pDCs), thymic pDCs constitutively express low levels of IFN-α. This leads to induction of interferon secondary genes (ISGs) in medullary thymocytes, raising the question whether IFN-α may play a role in T-cell development. When characterizing further differences between peripheral and thymic pDCs, we found that thymic pDCs have a phenotype consistent with an "activated signature" including expression of TNF-α and bone marrow stromal cell antigen 2 (BST2), but no expression of ILT7. Given that BST2 is induced by IFN-α, and IFN-α secretion is controlled by interaction between ILT7 and BST2, this regulatory pathway is apparently lost in thymic pDCs. Further, we also show that BST2 is constitutively expressed on a subset of medullary thymocytes at the mRNA and protein level reflecting a history of IFN-α transduced signals. The majority of BST2(+) thymocytes express CCR5 rendering them prevalent targets for R5-tropic HIV infection. Moreover, BST2(+) thymocytes express Foxp3 and CD25, consistent with the phenotype of natural Treg cells, and exert suppressive activity as they impair the proliferation of autologous CD3(+) thymocytes. Collectively, our results suggest that low levels of IFN-α secreted by thymic pDCs play an important role in the development of natural Treg cells
AB - In contrast to peripheral plasmacytoid DCs (pDCs), thymic pDCs constitutively express low levels of IFN-α. This leads to induction of interferon secondary genes (ISGs) in medullary thymocytes, raising the question whether IFN-α may play a role in T-cell development. When characterizing further differences between peripheral and thymic pDCs, we found that thymic pDCs have a phenotype consistent with an "activated signature" including expression of TNF-α and bone marrow stromal cell antigen 2 (BST2), but no expression of ILT7. Given that BST2 is induced by IFN-α, and IFN-α secretion is controlled by interaction between ILT7 and BST2, this regulatory pathway is apparently lost in thymic pDCs. Further, we also show that BST2 is constitutively expressed on a subset of medullary thymocytes at the mRNA and protein level reflecting a history of IFN-α transduced signals. The majority of BST2(+) thymocytes express CCR5 rendering them prevalent targets for R5-tropic HIV infection. Moreover, BST2(+) thymocytes express Foxp3 and CD25, consistent with the phenotype of natural Treg cells, and exert suppressive activity as they impair the proliferation of autologous CD3(+) thymocytes. Collectively, our results suggest that low levels of IFN-α secreted by thymic pDCs play an important role in the development of natural Treg cells
U2 - https://doi.org/10.1002/eji.201444787
DO - https://doi.org/10.1002/eji.201444787
M3 - Article
C2 - 25408362
SN - 0014-2980
VL - 45
SP - 728
EP - 737
JO - European journal of immunology
JF - European journal of immunology
IS - 3
ER -