Developmentally regulated fetal thymic and extrathymic T-cell receptor gamma delta gene expression.

Carding, Simon R.; Kyes, Susan; Jenkinson, Eric J.; Kingston, Rosetta; Bottomly, Kim; Owen, J. J. T.; Hayday, Adrian

doi:10.1101/gad.4.8.1304

Cited by 97 publications

(60 citation statements)

References 67 publications

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“…In murine influenza A infection, the number of ␥␦-T cells in the lung increased at a much higher rate after 7 days of viral infection (21). This finding suggests that the ␥␦-T cells in this disease are not only focused on the elimination of the virus-infected cells, but also on the repair processes of the host following a pathogen-inflicted injury.…”

Section: Discussionmentioning

confidence: 56%

Human γδ-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-β1 and Comparison with αβ-T Lymphocytes

Workalemahu

Foerster

Kroegel

et al. 2003

The Journal of Immunology

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T lymphocytes bearing the γδ-TCR accumulate during wound healing and inflammation. However, the role of γδ-T lymphocytes in fibrogenic tissue reactions is not well understood. Therefore, we addressed the question of whether human γδ-T cells express and synthesize connective tissue growth factor (CTGF), a factor known to regulate fibrogenesis and wound healing. In addition, the lymphoblastic leukemia T cell line (Loucy) that possesses characteristics typical of γδ-T cells was used as a model to evaluate the regulation of CTGF gene expression. Blood γδ-T cells isolated from healthy donors were grown in the presence of IL-15/TGF-β1 for 48 h and assessed for the expression and synthesis of CTGF. Nonstimulated human blood γδ-T cells and Loucy γδ-T cells expressed low levels of CTGF mRNA. Costimulation of the cells with IL-15 and TGF-β1 resulted in a substantially increased level of CTGF mRNA expression within 4–8 h, and it remained elevated for at least 48 h. In contrast, no CTGF mRNA was detected when nonstimulated and stimulated human CD4+ αβ-T cells were analyzed. In addition, Western blot analysis of human γδ-T cell lysates prepared 4 days following stimulation with IL-15 and TGF-β1 revealed a 38-kDa CTGF protein in cell lysates of human γδ-T cells. Detection was confirmed using Colo 849 fibroblasts, which can constitutively express high levels of CTGF. In conclusion, we herein present novel evidence that in contrast to CD4+ αβ-T cells human γδ-T cells are capable of expressing CTGF mRNA and synthesizing its corresponding protein, which supports the concept that γδ-T cells may contribute to wound healing or tissue fibrotic processes.

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Section: Discussionmentioning

confidence: 56%

Human γδ-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-β1 and Comparison with αβ-T Lymphocytes

Workalemahu

Foerster

Kroegel

et al. 2003

The Journal of Immunology

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“…cd TCR gene rearrangement can be detected by embryonic day 14 in the murine thymus 83 and week 8 in humans, 32 and canonical subsets can also be detected extrathymically during fetal development in both species. 83,84 The most striking feature is the change from having fairly diverse pairs of cd T cells (of which Vd1 1 serve as the majority in cord blood at birth) to increasingly restricted pairings, with Vc9Vd2 T cells becoming the major subset with very limited receptor diversity by adulthood (Figure 2). 32 By 1 year of life, the majority of peripheral blood Vc9Vd2 T cells are non-naive, readily produce IFNc upon stimulation and have cytolytic granules.…”

Section: Rites Of Passagementioning

confidence: 97%

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

2012

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The elusive task of defining the character of cd T cells has been an evolving process for immunologists since stumbling upon their existence during the molecular characterization of the a and b T cell receptor genes of their better understood brethren. Defying the categorical rules used to distinctly characterize lymphocytes as either innate or adaptive in nature, cd T cells inhabit a hybrid world of their own. At opposing ends of the simplified spectrum of modes of antigen recognition used by lymphocytes, natural killer and ab T cells are particularly well equipped to respond to the 'missing self' and the 'dangerous non-self', respectively. However, between these two reductive extremes, we are chronically faced with the challenge of making peace with the 'safe non-self' and dealing with the inevitable 'distressed self', and it is within this more complex realm cd T cells excel thanks to their highly empathetic nature. This review gives an overview of the latest insights revealing the unfolding story of human cd T cells, providing a biographical sketch of these unique lymphocytes in an attempt to capture the essence of their fundamental nature and events that influence their life trajectory. What hangs in their balance is their nuanced ability to differentiate the friends from the foe and the pathological from the benign to help us adapt swiftly and efficiently to life's many stresses. Keywords: antigen recognition; danger-associated molecular patterns; gamma delta T cell subsets; immune homeostasis; innate immunity; stress response PROLOGUE Since the time of their accidental discovery during the molecular characterization of the a and b T cell receptor (TCR) genes belonging to their relatively unambiguous brethren, 1 'enigmatic' is still one of the most commonly used adjectives to describe cd T cells. This can be attributed to the fact that these unconventional lymphocytes have thus far been remarkably successful in thwarting most attempts at definition. Much of what we know about T cell biology and function comes from what has been discerned through studies done on ab T cells; however, one thing that is certain is that the majority of the rules governing the lives of ab T cells are surprisingly irrelevant when it comes to understanding the elusive character of cd T cells. Table 1 highlights some of the major differences between these two T cell subsets in humans.Recognition by cd T cells is not typically in the context of classical major histocompatibility complex (MHC) class I or II molecules and neither is antigen processing required. 2,3 These observations are corroborated by the fact that the majority of cd T cells are CD8 and CD4 negative. Crystal structure analysis of the cd TCR determined that the length and conformation of cd TCR resemble immunoglobulins (Ig) more than the ab TCR, which was taken to suggest that antigen recognition by cd T cells may be more similar to the binding of antibody to antigen rather than the MHC/peptide complex recognized by ab T cells. 4 The very basis of foreign antigen rec...

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“…The expression ofIL4 mRNA by thymocytes in vivo during fetal ontogeny (13), and the secretion of 11,4 by fetal and adult CD4 -CD8 -(double-negative) thymocytes after in vitro activation (14,15), suggest that this cytokine may also have a role in normal T cell development . A number of in vitro studies have documented that IL4 can either augment or inhibit the growth of isolated thymocytes, depending on the cell population studied, the stimulus used for cell activation, and which other cytokines are present (15)(16)(17)(18)(19)(20) .…”

Section: Discussionmentioning

confidence: 99%

Interleukin 4 expressed in situ selectively alters thymocyte development.

Lewis

Forbush

et al. 1991

The Journal of Experimental Medicine

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SummaryUsing a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization ofcalcium mediated by these receptors. In contrast, transgenic single-positive (CD4+CD8 -and CD4 -CD8+) thymocytes and peripheral T cells exhibit decreased TCRmediated calcium mobilization. The development of CD4 -CD8+ thymocytes is significantly perturbed by 114 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4 -CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers ofB cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that 114 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.

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Developmentally regulated fetal thymic and extrathymic T-cell receptor gamma delta gene expression.

Cited by 97 publications

References 67 publications

Human γδ-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-β1 and Comparison with αβ-T Lymphocytes

Human γδ-T Lymphocytes Express and Synthesize Connective Tissue Growth Factor: Effect of IL-15 and TGF-β1 and Comparison with αβ-T Lymphocytes

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

Interleukin 4 expressed in situ selectively alters thymocyte development.

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