Dataset Information

Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA.

ABSTRACT: The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56⁺ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56⁺ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.

SUBMITTER: Tian Y

PROVIDER: S-EPMC5684192 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA.

Tian Yuan Y Babor Mariana M Lane Jerome J Schulten Veronique V Patil Veena S VS Seumois Grégory G Rosales Sandy L SL Fu Zheng Z Picarda Gaelle G Burel Julie J Zapardiel-Gonzalo Jose J Tennekoon Rashika N RN De Silva Aruna D AD Premawansa Sunil S Premawansa Gayani G Wijewickrama Ananda A Greenbaum Jason A JA Vijayanand Pandurangan P Weiskopf Daniela D Sette Alessandro A Peters Bjoern B

Nature communications 20171113 1

The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two m ...[more]

PMID: 29133794

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Project description:Many aged individuals develop monoclonal expansions of CD8 T cells. These expansions are derived from a CD8 memory T cell that outcompetes neighboring CD8 T cells. The molecular alterations within clonal expansions that confer this competitive advantage relative to other CD8 T cells remains unknown. These microarray experiments were designed to identify genes differentially expressed in age-associated expansions of CD8 memory T cells relative to polyclonal CD8 memory T cells found in the same aged mice. Subsequent analysis of these data identified two major types of clonal expansions, distinguished by expression level of integrin a4 mRNA and protein. Based on this classification, Expansion_rep1 belongs to the integrin a4 high subtype of clonal expansions. In contrast, reps 2, 4, and 5 belong to the integrin a4 low subtype of clonal expansions. Given the divergent biological properties of these two subtypes of clonal expansions, we have focused genes differentially expressed between Expansion_rep 2, 4, and 5 and their paired PolyclonalAged samples. Experiment Overall Design: A total of 8 samples were analyzed for gene expression using the Affymetrix mouse genome 430 2.0 microarray platform. The experimental samples of interest were age-associated clonal expansions of CD8 memory T cells. We purified four clonal expansions from four independent, aged mice (indicated as "Expansion" rep1 2, 3, 4). For each clonal expansion of CD8 memory T cells that was purified, there was a paired control in which polyclonal CD8 memory T cells were harvested from the same aged mouse (denoted as "PolyclonalAged" rep1, 2, 3, 4). These paired samples allow one to consider gene expression changes from mice which have undergone the same age-associated changes in biology. The predominant comparison this study focused on was changes in gene expression between age-associated clonal expansions of CD8 memory T cells and their paired, polyclonal CD8 memory T cells. A total of 4 of these pairs were collected.

Dataset Information

Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA.

Publications

Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA.

Similar Datasets

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