Interleukin 15 upregulates the expression of PD-1 and TIM-3 on CD4 + and CD8 + T cells
Mohamad S Hakim 1 2 , Rizka O A Jariah 3 , Michelle Spaan 4 , Andre Boonstra 4
Affiliations
Affiliations
1
Department of Microbiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada Yogyakarta, Indonesia.
2
Postgraduate School of Molecular Medicine, Erasmus MC-University Medical Center Rotterdam The Netherlands.
3
Department of Health Science, Faculty of Vocational Studies, Universitas Airlangga Surabaya, Indonesia.
4
Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam The Netherlands.
PMID: 32704430 PMCID: PMC7364376
Abstract
Virus-specific T cell-mediated immunity is severely impaired in chronic hepatitis B virus (HBV) patients. HBV-specific T cells in chronic HBV patients show a low ability to produce cytokines and to exert their cytotoxic activity. A prominent characteristic of these exhausted T cells is overexpression of inhibitory receptor molecules which negatively regulate T cell function. In this study, we examined in vitro regulation of two inhibitory receptor expressions, programmed death 1 (PD-1) and T cell immunoglobulin mucin domain-containing molecule 3 (TIM-3). Peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals were in vitro stimulated with a panel of cytokines. PD-1 and TIM-3 expression levels on CD4+ and CD8+ T cells were examined at days 2 and 7 post stimulation. We demonstrated that PD-1 and TIM-3 were induced via polyclonal (anti-CD3) and cytokine (interleukin 15 [IL-15]) stimulations. Noteworthy, there was a significantly increased induction of TIM-3 on CD8+ T cells as compared to CD4+ T cells. Our study thus contributes to further understanding the regulation of T cell exhaustion markers PD-1 and TIM-3.
Keywords: Inhibitory receptors; PD-1; T cells; TIM-3; interleukin 15.