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Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile.

ABSTRACT: gammadelta T lymphocytes in the intestinal intraepithelial layer (gammadelta IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of gammadelta IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8(+) alphabeta T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8(+) alphabeta T cells must be activated to become cytotoxic effectors, gammadelta IELs are constitutively activated and appear to use different signaling cascades. Our data suggest that gammadelta IELs may respond efficiently to a broad range of pathological situations irrespective of their diverse T cell antigen receptor repertoire. gammadelta IELs may modulate local immune responses and participate in intestinal lipid metabolism, cholesterol homeostasis, and physiology. This study provides a strong basis for further investigations of the roles of these cells as well as mucosal immune defense in general.

SUBMITTER: Fahrer AM

PROVIDER: S-EPMC56949 | biostudies-literature | 2001 Aug

REPOSITORIES: biostudies-literature

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Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile.

Fahrer A M AM Konigshofer Y Y Kerr E M EM Ghandour G G Mack D H DH Davis M M MM Chien Y H YH

Proceedings of the National Academy of Sciences of the United States of America 20010801 18

gammadelta T lymphocytes in the intestinal intraepithelial layer (gammadelta IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of gammadelta IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8(+) alphabeta T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8(+) alphabe ...[more]

PMID: 11526237

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Project description:Intraepithelial T lymphocytes (T-IELs), which constitute over 50% of the total T lymphocytes in the animal, patrol the mucosal epithelial lining to defend against pathogen invasion while maintaining gut homeostasis. In addition to expressing T cell markers such as CD4 and CD8, T-IELs display T cell receptors (TCR), including either TCRαβ or TCRγδ. Both humans and mice share similar T-IEL subsets: TCRγδ+, TCRαβ+CD8αα+, TCRαβ+CD4+, and TCRαβ+CD8αβ+. Among these subsets, human T-IELs are predominantly TCRαβ+ (over 80%), whereas those in mice are mostly TCRγδ+ (~60%). Of note, the majority of the TCRγδ+ subset expresses CD8αα in both species. Although T-IELs have been extensively studied in humans and mice, their profiles in cattle have not been well examined. Our study is the first to characterize bovine T-IELs using flow cytometry, where we identified several distinct features. The percentage of TCRγδ+ was comparable to that of TCRαβ+ T-IELs (both ~50% of CD3+), and the majority of bovine TCRγδ+ T-IELs did not express CD8 (CD8-) (above 60%). Furthermore, about 20% of TCRαβ+ T-IELs were CD4+CD8αβ+, and the remaining TCRαβ+ T-IELs were evenly distributed between CD4+ and CD8αβ+ (~40% of TCRαβ+ T-IELs each) with no TCRαβ+CD8αα+ identified. Despite these unique properties, bovine T-IELs, similar to those in humans and mice, expressed a high level of CD69, an activation and tissue-retention marker, and a low level of CD62L, a lymphoid adhesion marker. Moreover, bovine T-IELs produced low levels of inflammatory cytokines such as IFNγ and IL17A, and secreted small amounts of the immune regulatory cytokine TGFβ1. Hence, bovine T-IELs' composition largely differs from that of human and mouse, with the dominance of the CD8- population among TCRγδ+ T-IELs, the substantial presence of TCRαβ+CD4+CD8αβ+ cells, and the absence of TCRαβ+CD8αα+ T-IELs. These results provide the groundwork for conducting future studies to examine how bovine T-IELs respond to intestinal pathogens and maintain the integrity of the gut epithelial barrier in animals.

Dataset Information

Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile.

Publications

Attributes of gammadelta intraepithelial lymphocytes as suggested by their transcriptional profile.

Similar Datasets

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