Biomedical subjects

Tatyana Chtanova

Publications and source records attributed to Tatyana Chtanova.

6 recordsLinked to original sources

PubMed2006

Immune cell transcriptome datasets reveal novel leukocyte subset-specific genes and genes associated with allergic processes.

BACKGROUND: The precise function of various resting and activated leukocyte subsets remains unclear. For instance, mast cells, basophils, and eosinophils play important roles in allergic inflammation but also participate in other immunologic responses. One strategy to understand leukocyte subset function is to define the expression and function of subset-restricted molecules. OBJECTIVE: To use a microarray dataset and bioinformatics strategies to identify novel leukocyte markers as well as genes associated with allergic or innate responses. METHODS: By using Affymetrix microarrays, we generated an immune transcriptome dataset composed of gene profiles from all of the major leukocyte subsets, including rare enigmatic subsets such as mast cells, basophils, and plasma cells. We also assessed whether analysis of genes expressed commonly by certain groups of leukocytes, such as allergic leukocytes, might identify genes associated with particular responses. RESULTS: Transcripts highly restricted to a single leukocyte subset were readily identified (>2000 subset-specific transcripts), many of which have not been associated previously with leukocyte functions. Transcripts expressed exclusively by allergy-related leukocytes revealed well known as well as novel molecules, many of which presumably contribute to allergic responses. Likewise, Nearest Neighbor Analysis of genes coexpressed with Toll-like receptors identified genes of potential relevance for innate immunity. CONCLUSION: Gene profiles from all of the major human leukocyte subsets provide a powerful means to identify genes associated with single leukocyte subsets, or different types of immune response. CLINICAL IMPLICATIONS: A comprehensive dataset of gene expression profiles of human leukocytes should provide new targets or biomarkers for human inflammatory diseases.

Gene Expression Profiling↗

PubMed2006

Thymocyte motility: mutants, movies and migration patterns.

Developing T cells are highly motile and undergo long-range migrations in the thymus as part of their developmental program. In the past two years, significant advances have been made in understanding the nature of the signals that control the entry of thymocyte progenitors into the thymus and the exit of mature thymocytes from the thymus. Progress has also been made in identifying the chemokine signals that control intrathymic migration patterns. In addition, the recent application of two-photon laser scanning microscopy has made it possible to make real-time observations of thymocytes within the three-dimensional environment of the thymus, and has shed new light on the relationship between positive selection and thymocyte migration.

Animals↗

PubMed2006

Thymic microenvironments for T cell differentiation and selection.

The adult thymus provides a variety of specialized microenvironments that support and direct T cell differentiation and selection. In this review, we summarize recent advances in the understanding of the function of microenvironments in shaping a diverse T cell repertoire. In particular, we focus on how thymocytes move in and out of these specialized thymic compartments in response to homing signals, differential chemokine gradients and other factors that regulate T cell migration. In addition, we discuss the diverse developmental signals provided by these microenvironments that contribute to the generation of divergent T cell lineages.

Animals↗

PubMed2005

Identification of T cell-restricted genes, and signatures for different T cell responses, using a comprehensive collection of microarray datasets.

We used a comprehensive collection of Affymetrix microarray datasets to ascertain which genes or molecules distinguish the known major subsets of human T cells. Our strategy allowed us to identify the genes expressed in most T cell subsets: TCR alphabeta+ and gammadelta+, three effector subsets (Th1, Th2, and T follicular helper cells), T central memory, T effector memory, activated T cells, and others. Our genechip dataset also allowed for identification of genes preferentially or exclusively expressed by T cells, compared with numerous non-T cell leukocyte subsets profiled. Cross-comparisons between microarray datasets revealed important features of certain subsets. For instance, blood gammadelta T cells expressed no unique gene transcripts, but did differ from alphabeta T cells in numerous genes that were down-regulated. Hierarchical clustering of all the genes differentially expressed between T cell subsets enabled the identification of precise signatures. Moreover, the different T cell subsets could be distinguished at the level of gene expression by a smaller subset of predictor genes, most of which have not previously been associated directly with any of the individual subsets. T cell activation had the greatest influence on gene regulation, whereas central and effector memory T cells displayed surprisingly similar gene expression profiles. Knowledge of the patterns of gene expression that underlie fundamental T cell activities, such as activation, various effector functions, and immunological memory, provide the basis for a better understanding of T cells and their role in immune defense.

Cluster Analysis↗

PubMed2004

B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells.

BAFF (B cell-activating factor belonging to the TNF family) is a cell survival and maturation factor for B cells, and overproduction of BAFF is associated with systemic autoimmune disease. BAFF binds to three receptors, BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA). Using specific mAbs, BAFF-R was found to be the predominant BAFF receptor expressed on peripheral B cells, in both humans and mice, and antagonist mAbs to BAFF-R blocked BAFF-mediated costimulation of anti- micro responses. The other BAFF receptors showed a much more restricted expression pattern, suggestive of specialized roles. BCMA was expressed by germinal center B cells, while TACI was expressed predominantly by splenic transitional type 2 and marginal zone B cells, as well as activated B cells, but was notably absent from germinal center B cells. BAFF was also an effective costimulator for T cells, and this costimulation occurs entirely through BAFF-R. BAFF-R, but not TACI or BCMA, was expressed on activated/memory subsets of T cells, and T cells from BAFF-R mutant A/WySnJ mice failed to respond to BAFF costimulation. Thus, BAFF-R is important not only for splenic B cell maturation, but is the major mediator of BAFF-dependent costimulatory responses in peripheral B and T cells.

Animals↗

PubMed2004

T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells.

Effector T cell responses have long been viewed in the context of the Th1/Th2 paradigm. Recently, a third major subset of nonpolarized effector T cells that provides help to B cells has been identified. These T cells, termed T follicular helper (T(FH)) cells, home to the B cell areas of secondary lymphoid tissue, through interactions mediated via the chemokine receptor CXCR5 and its ligand CXCL13. Affymetrix microarrays were used to identify transcription factors, cytokines, and cell surface molecules that underlie the differentiation pathways and functional properties of the T(FH) subset. The transcriptional profile of human CXCR5(+) T(FH) cells was compared with that of Th1 and Th2 cells, which enabled the identification of numerous genes expressed preferentially by T(FH) cells, over the other effector subsets. Certain T(FH) genes were also expressed by B cells and thus appear to be particularly relevant for humoral immunity. Abs were used to confirm the expression of several factors. In particular, CD84 and CD200, the cytokine IL-21, and the transcription factor BCL6 were all strongly associated with T(FH) cells. Gene microarrays reveal a highly distinctive transcriptional profile for a third subset of effector T cells that differs markedly from Th1 and Th2 cells.

Antigens, CD↗