Transcriptomics

Dataset Information

66

Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation


ABSTRACT: CD8+ T cells play a critical role in the immune response to viral pathogens. Persistent human CMV (HCMV) infection results in a strong increase in the number of virus-specific, quiescent effector-type CD8+ T cells with constitutive cytolytic activity, but the molecular pathways involved in the induction and maintenance of these cells are unknown. We show here that HCMV infection induced acute and lasting changes in the transcriptomes of virus-reactive T cells collected from HCMV-seropositive patients at distinct stages of infection. Enhanced cell cycle and metabolic activity was restricted to the acute phase of the response, but at all stages, HCMV-specific CD8+ T cells expressed the Th1-associated transcription factors T-bet (TBX21) and eomesodermin (EOMES), in parallel with continuous expression of IFNG mRNA and IFN-g–regulated genes. The cytolytic proteins granzyme B and perforin as well as the fractalkine-binding chemokine receptor CX3CR1 were found in virus-reactive cells throughout the response. During HCMV latency, virus-specific CD8+ T cells lacked the typical features of exhausted cells found in other chronic infections. Persistent effector cell traits together with the permanent changes in chemokine receptor usage of virus-specific, nonexhausted, long-lived CD8+ T cells may be crucial to maintain lifelong protection from HCMV reactivation. CD8+ T cells of naive, effector, and memory type were isolated from six latently chronic-infected healthy donors. For RNA isolation and microarray analysis, 3 independent donors and a pool of 3 additional healthy individuals were used. Total RNA of all naive CD8+ T cells was pooled and used as a common reference sample.

ORGANISM(S): Homo sapiens  

SUBMITTER: Perry D Moerland   Rene A van Lier  Kirsten M Hertoghs 

PROVIDER: E-GEOD-24151 | ArrayExpress | 2010-09-15

SECONDARY ACCESSION(S): GSE24151PRJNA130033

REPOSITORIES: GEO, ArrayExpress

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Publications

Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation.

Hertoghs Kirsten M L KM   Moerland Perry D PD   van Stijn Amber A   Remmerswaal Ester B M EB   Yong Sila L SL   van de Berg Pablo J E J PJ   van Ham S Marieke SM   Baas Frank F   ten Berge Ineke J M IJ   van Lier René A W RA  

The Journal of clinical investigation 20101101 11


CD8+ T cells play a critical role in the immune response to viral pathogens. Persistent human cytomegalovirus (HCMV) infection results in a strong increase in the number of virus-specific, quiescent effector-type CD8+ T cells with constitutive cytolytic activity, but the molecular pathways involved in the induction and maintenance of these cells are unknown. We show here that HCMV infection induced acute and lasting changes in the transcriptomes of virus-reactive T cells collected from HCMV-sero  ...[more]

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