BST2/Tetherin is constitutively expressed on human thymocytes with the phenotype and function of Treg cells.

ABSTRACT: In contrast to peripheral plasmacytoid DCs (pDCs), thymic pDCs constitutively express low levels of IFN-?. This leads to induction of interferon secondary genes (ISGs) in medullary thymocytes, raising the question whether IFN-? 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-? and bone marrow stromal cell antigen 2 (BST2), but no expression of ILT7. Given that BST2 is induced by IFN-?, and IFN-? 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-? 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-? secreted by thymic pDCs play an important role in the development of natural Treg cells.

SUBMITTER: Epeldegui M 

PROVIDER: S-EPMC4361012 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature