Oncotarget

Research Papers:

Chronic activation profile of circulating CD8+ T cells in Sézary syndrome

Marina Passos Torrealba _, Kelly Cristina Manfrere, Denis R. Miyashiro, Josenilson F. Lima, M. Oliveira, Nátalli Z. Pereira, Jade Cury-Martins, Juliana Pereira, Alberto J.S. Duarte, Maria N. Sato and José A. Sanches

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Oncotarget. 2018; 9:3497-3506. https://doi.org/10.18632/oncotarget.23334

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Abstract

Marina Passos Torrealba1, Kelly Cristina Manfrere1, Denis R. Miyashiro2, Josenilson F. Lima1, Luana de M. Oliveira1, Nátalli Z. Pereira1, Jade Cury-Martins2, Juliana Pereira3, Alberto J.S. Duarte1, Maria N. Sato1,* and José A. Sanches2,*

1Medical Investigation Laboratory (LIM-56), Tropical Medicine Institute of São Paulo, Department of Dermatology, University of São Paulo Medical School, São Paulo, Brazil

2Cutaneous Lymphoma Clinic, Hospital das Clinicas, Department of Dermatology, University of São Paulo Medical School, São Paulo, Brazil

3Hematology Department, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil

*These authors share the mentorship, critical revision and supervision of this study

Correspondence to:

Marina Passos Torrealba, email: [email protected]

Keywords: Sézary syndrome; CD8+ T cells; chronic activation markers; sCD38; sCD127

Received: October 12, 2017     Accepted: December 01, 2017     Published: December 16, 2017

ABSTRACT

Sézary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sézary cells have been studied extensively, studies on adaptive immunity regarding CD8+T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Rα axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum. Although the SS patients of our cohort had reduced numbers of CD8+ T cells, they exhibited higher percentages of CD8+CD38+ T cells, mainly effector/memory CD8+ T cells, than the control group. In contrast, down-regulated expression of the activation markers CD127/IL-7R and CD26 was found in the CD8+ T cells of SS patients. High serum levels of sCD38 and sCD127 and scarce serum levels of IL-7 were detected, emphasizing the immune activation status of SS patients. Moreover, CD8+ T cells from SS patients exhibited IL-7 unresponsiveness to STAT5 phosphorylation and Bcl-2 expression, and IL-7 priming partially restored IFNγ production. Our findings showed a chronic activation profile of CD8+ T cells, as an attenuated cytotoxic profile and impaired IL-7 responsiveness was observed, suggesting chronic activation status of CD8+ T cells in SS patients.


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