Enhancement of the TCRζ Expression, Polyclonal Expansion, and Activation of T Cells from Patients with Acute Myeloid Leukemia After IL-2, IL-7, and IL-12 Induction.

DNA AND CELL BIOLOGY(2015)

Cited 12|Views55
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Abstract
Defective T cell receptor (TCR) signaling resulting in lower T cell function plays a crucial role in the pathogenesis of T cell immunodeficiency in leukemia. Previous studies have indicated that lower TCR levels are a common characteristic of patients with leukemia, and upregulating TCR could partially recover T cell function. In this study, we characterized the effect of the stimulating factor induction on the TCR, Zap-70, and FcRI levels, IFN- secretion, and the distribution and clonal expansion of TCR V subfamilies in CD3(+) T cells sorted from peripheral blood from acute myeloid leukemia (AML) patients. The induction included single stimulating factor or a combination with different cytokines (IL-2, IL-7, IL-2+IL-7, IL-7+IL-12, CD3, CD3+CD28 antibody, CD3+CD28 antibody+IL-2, and CD3+CD28 antibody+IL-7) at 72h. The results showed that increased TCR and Zap-70 levels with deceased FcRI in T cells after induction, and different responses to cytokine in T cell from different cases may indicate the heterogeneity of T cells and different immune statuses in different AML cases. Increased IFN- levels in T cells from AML patients were detected after induction in the IL-12+IL-7, CD3+CD28+IL-2, and CD3+CD28+IL-7 groups. Moreover, the number of TCR V subfamily T cells expressed was increased; however, all of the TCR V subfamily T cells in the AML patients could not be completely recovered after induction. In conclusion, the cytotoxicity and activation function of T cells could be enhanced after induction by different stimuli accompanied by an increase in TCR and Zap-70 and recovery of the TCR V repertoire in AML patients.
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Key words
acute myeloid leukemia,tcrζ expression
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