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The fine control of T-cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B-lymphocyte-induced maturation protein-1 (Blimp-1/Prdm1) is highly expressed in CD4(+) T cells from chronically HIV-infected (CHI) patients compared to cells from long-term nonprogressors or healthy controls. Stimulation through the T-cell receptor in the presence of IL-2 induces Blimp-1 protein expression. We show here that Blimp-1 levels are translationally regulated by microRNA-9 (miR-9). Overexpression of miR-9 induces Blimp-1 repression, restoring IL-2 secretion in CD4(+) T cells via reduction in the binding of Blimp-1 to the il-2 promoter. In CHI patients where IL-2 expression is reduced and there is generalized T-cell dysfunction, we show differential expression of both miR-9 and Blimp-1 in CD4(+) cells compared with levels in long-term nonprogressors. These data identify a novel miR-9/Blimp-1/IL-2 axis that is dysregulated in progressive HIV infection.

Original publication

DOI

10.1002/eji.201242695

Type

Journal article

Journal

Eur J Immunol

Publication Date

02/2013

Volume

43

Pages

510 - 520

Keywords

Adult, B-Lymphocytes, CD4-Positive T-Lymphocytes, Cell Differentiation, Cell Line, Tumor, Down-Regulation, Female, HIV Infections, Humans, Interleukin-2, Jurkat Cells, Male, MicroRNAs, Middle Aged, Positive Regulatory Domain I-Binding Factor 1, Programmed Cell Death 1 Receptor, Receptors, Antigen, T-Cell, Repressor Proteins, Up-Regulation, Young Adult