T‐bet is a key regulator for the lineage commitment in CD4 T helper (Th) 1 cells by activating the hallmark production of interferon‐γ, and its expression level is linked to autoimmune, infectious, and allergic diseases. A T to C base substitution has been identified at position ‐1993 in the TBX21 (encoding T‐bet) promoter and has been associated with asthma and systemic lupus erythematosus. This study aimed to investigate the molecular mechanisms responsible for the influence of the T‐1993C polymorphism on transcription and its functional effect by luciferase reporter, EMSAs, Chromatin immunoprecipitation assay, and flow cytometric analysis of intracellular T‐bet, IFN‐γ and IL‐4 expression in activated CD4+ T cells. The presence of a ‐1993T allele obviously increases promoter activity compared with that of a promoter with a ‐1993C allele. TBX21 promoter carrying ‐1993C allele possesses significantly stronger binding affinity to the Yin Yang 1 (YY1) transcription factor than that carrying ‐1993T allele. YY1 overexpression decreased TBX21 promoter function in a T cell line, demonstrating that this element functions as a repressor. The C to T base exchange relieves the repression mediated by YY1. The individuals carrying ‐1993C allele were determined to have significantly diminished expression of TBX21 and IFN‐γ and increased IL‐4 production in cells compared with the individuals carrying ‐1993T allele (P < 0.05). These findings demonstrate that the TBX21 T‐1993C polymorphism represses TBX21 expression and Th1 cytokine production through control of YY1, which might result in the imbalance between Th1 and Th2 immune responses in autoimmune or allergic diseases.

ABSTRACT. To screen the nucleic acid aptamers of the EB virus-positive nasopharyngeal carcinoma cells, we used SELEX technology and synthesized in vitro a 78-nucleotide random DNA library. We used normal nasopharyngeal epithelial cells and EB virus-positive low differentiated nasopharyngeal carcinoma cells as target to conduct 10 cycles of screening, cloning, sequencing, and identification of the aptamers. The fluorescence produced by the combination of the sub-library and the target cells gained intensity gradually with the increase in the number of screening cycles, indicating elevated binding capacity. The cluster analysis showed that the aptamers can be divided into three families, with two of the families having the common conserved sequence. In this study, by screening nucleic acid aptamers for affinity and specificity, we established an initial aptamer library for EB virus-positive nasopharyngeal carcinoma cells.