Abstract

To study the peripheral blood T-cell subsets and regulatory T-cells of multiple myeloma (MM) patients. 48 MM patients and 24 healthy controls were enrolled. Changes in peripheral blood T-cell subsets in the MM patients i.e. CD4+CD25+T cells and CD4+CD25+CD127lowT regulatory cells (CD4+CD25+CD127lowTregs) and in healthy controls were measured using flow cytometry and immunohischemistry. The total T-cells (CD3+) in peripheral blood lymphocyte and auxiliary/induced T-cells (CD3+CD4+ T cell) of the 48 MM patients showed no statistical significance when compared with those of the control group. Suppressor/cytotoxicity T-cells (CD3+CD8+ T cell) increased (p < 0.05). CD4+CD25+T cells and CD4+CD25+CD127low Tregs were significantly higher than corresponding values in the healthy group (p < 0.05). The CD4+/CD8+ T cell ratio of Stage III MM patients was significantly lower than that of the control group (p < 0.05). The CD4+CD25+T cells and CD4+CD25+CD127low Tregs of MM patients in the stable and the progressive stages were significantly higher than those of MM patients in the control group (p < 0.05). The abnormality of the peripheral blood T-cell subset, increased expression of CD4+CD25+CD127low Tregs, and low cellular immunity of MM patients are related to clinical staging and progression of the disease. The quantity of CD4+CD25+CD127lowTregs of peripheral blood cells of MM patients could be significantly increased through the inhibition of CD4+ and CD8+T cell activities. CD4+CD25+CD127low Tregs promotes tumor growth through the inhibition of immunologic cell proliferation. Immunological dysfunction based on Tregs cells plays an important role in the pathogenic course.

Highlights

  • Multiple myeloma (MM), a clonal disease associated with plasma cell abnormality, results in renal damage and bone destruction

  • A comparison of peripheral blood T-cell subsets of MM patients and the healthy control group showed that the CD4+T cell percentage of MM patients and the healthy control group had no statistically significant difference (p > 0.05), while the CD8+T cell level of MM patients was significantly higher than that of the control group (p 0.05). (A) = CD4+T cells in MM patients; (B) = CD4+T cells in healthy control; (C) = CD8+T cells in MM patients; (D) = CD8+T cells in healthy control

  • With the continuous developments in molecular biology and immunology, mechanisms related to immunological dysfunction have been gradually revealed in recent years

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Summary

Introduction

Multiple myeloma (MM), a clonal disease associated with plasma cell abnormality, results in renal damage and bone destruction. Lymphocytes involved in immune responses play an important role in MM incidence. T-regulatory cells (Tregs) are involved in the negative regulation of the immune system. They play an important role in tumor immuno-suppression and immune escape [4]. The negative immune regulation mechanisms of Tregs occur through many routes such as the direct killing of effector T-cells by contacting sthem , or dendritic cells (DC), and activating the Fas/FasL signal pathway; inducing effector Tcell apoptosis through the competitive binding of high expression CD25+ molecules (IL-2 receptor) and IL-2; and inhibiting multiple immune cells by secreting inhibitory cytokines (TGF-β and IL-10) (5 – 7). Recent studies indicate that the specific expression of CD4+CD25+ Tregs transcription factor Foxp is responsible for the development, activation, and functioning of Tregs, and is considered to be a specific marker of Tregs [8, 9]. The application of CD127, a cell-surface antigen, provides more convenient and effective means of detecting CD4+CD25+Tregs

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