Abstract

We aim to investigate the effects of Tim-3 and programmed cell death-1 (PD-1) on the monocytes and T lymphocytes in septic patients. Expression of Tim-3 and PD-1 on the CD3, CD4, and CD8 lymphocytes and monocytes was determined using flow cytometry. CBA technique was utilized to determine the expression of cytokines in the lymphocyte supernatant in addition to the IL-10 and TNF-α positivity in monocytes in the presence of Tim-3 and/or PD-1 receptor blockade. Compared with the normal control, significant elevation was observed in the expression of PD-1 on CD3 (P = 0.004), CD4, and CD8 monocytes. Blockade of the Tim-3 signaling pathway contributed to the significant elevation of IL-10 and TNF-α in the supernatant of T lymphocytes in the septic patients, while the PD-1 signaling pathway blockade only triggered the obvious elevation of TNF-α in the T lymphocytes. Blockade of Tim-3 and PD-1 induced the positivity of IL-10- and TNF-α-expressing cells in the peripheral monocytes. Significant changes were noticed in the Tim-3 and PD-1 in the T lymphocytes and monocytes. Blockade of Tim-3 and PD-1 contributed to the function of lymphocytes and monocytes. In the septic process, Tim-3 and PD-1 played crucial roles in the immune response of T lymphocytes and monocytes.

Highlights

  • Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection [1], is still a challenge as it is one of the leading causes for mortality in ICU despite the advances in the diagnosis and treatment of such disease [2,3,4,5]

  • We aim to investigate the expression of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) and programmed death-1 (PD-1) in T lymphocytes and monocytes of the peripheral blood in septic patients

  • We found that the expression of Tim-3 and PD-1 showed significant changes in the T lymphocytes and monocytes in the peripheral blood in septic patients

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Summary

Introduction

A life-threatening organ dysfunction caused by a dysregulated host response to infection [1], is still a challenge as it is one of the leading causes for mortality in ICU despite the advances in the diagnosis and treatment of such disease [2,3,4,5]. Extensive studies have been performed to investigate the pathogenesis of sepsis which are aimed at facilitating the diagnosis and treatment, as well as improving the survival rates. Tim-3 and PD-1 have been reported to be closely involved in the pathogenesis of tumor, autoimmune diseases, and chronic viral diseases [11,12,13,14,15,16,17] These two factors mediated the functional failure of T lymphocytes, and several studies have been carried out to determine their roles in sepsis; the exact mechanisms are still not well defined [18]

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