Induced Sézary syndrome PBMCs poorly express immune response genes up-regulated in stimulated memory T cells☆

Abstract 

Background

Dysfunctions in memory T cells contribute to various inflammatory autoimmune diseases and neoplasms. We hypothesize that investigating the differences of genetic profiles between resting and activated naïve and memory T cells may provide insight into the characterization of abnormal memory T cells in diseases, such as Sézary syndrome (SS), a neoplasm composed of CD4⁺ CD45RO⁺ cells.

Objective

We determined genes distinctively expressed between resting and activated naive and memory cells. Levels of up-regulated genes in resting and activated memory cells were measured in SS PBMCs, which were largely comprised of CD4⁺ CD45RO⁺ cells, to quantitatively assess how different Sézary cells were from memory cells.

Methods

We compared gene expression profiles using high-density oligo-microarrays between resting and activated naïve and memory CD4⁺ T cells. Differentially expressed genes were confirmed by qRT-PCR and immunoblotting. Levels of genes up-regulated in activated and resting memory T cells were determined in SS PBMCs by qRT-PCR.

Results

Activated memory cells expressed greater numbers of immune-mediated genes involved in effector function compared to naïve cells in our microarray analysis and qRT-PCR. Nine out of 14 genes with enhanced levels in activated memory cells had reduced levels in SS PBMCs (p<0.05).

Conclusions

Activation of memory and naïve CD4⁺ T cells revealed a diverging gap in gene expression between these subsets, with memory cells expressing immune-related genes important for effector function. Many of these genes were markedly depressed in SS patients, implying Sézary cells are markedly impaired in mounting immune responses compared to memory cells.

Keywords: T cells, Activation, Memory, CD4/helper T cells, Sézary syndrome