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Distinct gene expression profiles of human type 1 and type 2 T helper cells.

ABSTRACT: BACKGROUND:The development and activation of CD4+ helper T cell (Th) subsets with distinct patterns of unbalanced production of cytokines play an important part in infectious, allergic and autoimmune diseases. Human neonatal cord blood CD4+ Th cells can be polarized into type 1 or type 2-like effector cells in vitro by culturing them in the presence of interleukin (IL)-12 or IL-4, respectively. We have exploited this experimental system to identify marker genes that are differentially expressed by polarized Th1 and Th2 cells. An oligonucleotide microarray specifically designed to screen for inflammation-related candidate genes was used and the differential expression was further validated with a quantitative real-time RT-PCR method. RESULTS:In addition to the previously described marker genes of Th cells, we report subtle changes in the expression of several other genes that represent growth factors, receptors and other signaling molecules in polarized Th1 and Th2 cell subsets. Additionally, we describe a novel set of genes as Th1/Th2 differentiation markers for cells activated by anti-CD3 and anti-CD28 antibodies. CONCLUSIONS:This study demonstrates the power of the targeted use of microarrays in combination with quantitative real-time RT-PCR in identifying and validating new marker genes for gene expression studies.

SUBMITTER: Hamalainen H

PROVIDER: S-EPMC55319 | biostudies-literature | 2001

REPOSITORIES: biostudies-literature

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Distinct gene expression profiles of human type 1 and type 2 T helper cells.

Hamalainen H H Zhou H H Chou W W Hashizume H H Heller R R Lahesmaa R R

Genome biology 20010621 7

<h4>Background</h4>The development and activation of CD4+ helper T cell (Th) subsets with distinct patterns of unbalanced production of cytokines play an important part in infectious, allergic and autoimmune diseases. Human neonatal cord blood CD4+ Th cells can be polarized into type 1 or type 2-like effector cells in vitro by culturing them in the presence of interleukin (IL)-12 or IL-4, respectively. We have exploited this experimental system to identify marker genes that are differentially ex ...[more]

PMID: 11516335

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Project description:Natural killer (NK) cells during chronic viral infection have been well studied in the past. We performed an unbiased next-generation RNA-sequencing approach to identify commonalities or differences of the effect of HIV, HCV, and HBV viremia on NK cell transcriptomes. Using cell sorting, we obtained CD3- CD56+ NK cells from blood of 6 HIV-, 8 HCV-, and 32 HBV-infected patients without treatment. After library preparation and sequencing, we used an in-house analytic pipeline to compare expression levels with matched healthy controls. In NK cells from HIV-, HCV-, and HBV-infected patients, transcriptome analysis identified 272, 53, and 56 differentially expressed genes, respectively (fold change, >1.5; q-value, 0.2). Interferon-stimulated genes were induced in NK cells from HIV/HCV patients, but not during HBV infection. HIV viremia downregulated ribosome assembly genes in NK cells. In HBV-infected patients, viral load and alanine aminotransferase (ALT) variation had little effect on genes related to NK effector function. In conclusion, we compare, for the first time, NK cell transcripts of viremic HIV, HCV, and HBV patients. We clearly demonstrate distinctive NK cell gene signatures in three different populations, suggestive for a different degree of functional alterations of the NK cell compartment compared to healthy individuals.IMPORTANCE Three viruses exist that can result in persistently high viral loads in immunocompetent humans: human immunodeficiency virus (HIV), hepatitis C virus, and hepatitis B virus. In the last decades, by using flow cytometry and in vitro assays on NK cells from patients with these types of infections, several impairments have been established, particularly during and possibly contributing to HIV viremia. However, the background of NK cell impairments in viremic patients is not well understood. In this study, we describe the NK cell transcriptomes of patients with high viral loads of different etiologies. We clearly demonstrate distinctive NK cell gene signatures with regard to interferon-stimulated gene induction and the expression of genes coding for activation markers or proteins involved in cytotoxic action, as well immunological genes. This study provides important details necessary to uncover the origin of functional and phenotypical differences between viremic patients and healthy subjects and provides many leads that can be confirmed using future in vitro manipulation experiments.

Dataset Information

Distinct gene expression profiles of human type 1 and type 2 T helper cells.

Publications

Distinct gene expression profiles of human type 1 and type 2 T helper cells.

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