Upregulated TCRζ improves cytokine secretion in T cells from patients with AML
- Shaohua Chen†1,
- Xianfeng Zha†2,
- Li Shi1,
- Lingling Zhou1,
- Lijian Yang1,
- Bo Li1,
- Xiuli Wu1,
- Jun Zhong3,
- Tao Zhang3,
- Yuhong Lu3,
- Kanger Zhu3 and
- Yangqiu Li1, 4Email author
© Chen et al. 2015
Received: 24 May 2015
Accepted: 5 June 2015
Published: 18 June 2015
Previous studies indicated that upregulating TCRζ partially recovers T cell function in patients with leukemia. In this study, we characterized the cytokine profile of TCRζ-transfected T cells from acute myeloid leukemia (AML) patients by Quantibody®Array Glass Chip. Firstly, the significantly lower expression of TCRζ in CD3+/TCRζ+ cells from AML patients was found. Increased secretion of IL-2, IL-8, IL-10, IL-13, IFN-γ, TNF-α, GM-CSF, growth-regulated oncogene (GRO), MIP-1b, and regulated on activation, normal T cell expressed and secreted (RANTES) could be detected in T cells from AML patients after TCRζ upregulating. We concluded that upregulating TCRζ in T cells from AML can alter the secretion profile of cytokines and chemokine which are involved in T cell proliferation and activation.
Acute myeloid leukemia (AML) is an aggressive disease with an unfavorable prognosis [1–3]. T cell immunodeficiency is a common characteristic in hematological malignancies which may be due to defective TCRζ. Previous studies showed that TCRζupregulation could be induced in CD3+T cells from AML patients by IL-2, IL-7, and IL-12 . In this study, we characterized the secretion profile of cytokines and chemokines related to T cell activation in TCRζ-IRES2-EGFP-transfected T cells from AML patients after TCRζupregulation.
CD3+T cells were sorted from PBMCs from four AML patients (Additional file 1: Table S1) who had TCRζ deficiency and then transfected with TCRζ-IRES2-EGFP or IRES2-EGFP, respectively, by nucleofection . Significant upregulation of TCRζ in TCRζ-IRES2-EGFP-transfected CD3+T cells was confirmed. Similar results were found in TCRζ downstream target factor Zap-70 (Fig. 1d–f). Thus, TCRζ gene transfection could directly upregulate TCRζ and Zap-70 in T cells from AML patients as previously found in CML .
In conclusion, we characterized the profile of cytokines and chemokines secretion in T cells after TCRζ gene transfection. Most cytokines related to T cell proliferation and activation, such as IL-2, IFN-γ, and TNF-α, had increased secretion after TCRζ upregulating. Moreover, some of the Th1-associated CC subfamily chemokines, such as CCL4 and CCL5, may contribute to T cell activation via TCRζ upregulation. These results may further support the idea of the effects of upregulating TCRζ in T cell immunity.
This study was supported by grants from the National Natural Science Foundation of China (Nos. 81100353, 81270604, and 81400109), the China Postdoctoral Science Foundation (No. 2013 M540685), the Guangdong Natural Science Foundation (Nos. S2013040016151 and S2013020012863), the Foundation for High-level Talents in Higher Education of Guangdong, China (No. 246-54), the Medical Science Foundation of Guangdong Province (Nos.A2011325 and B2013213), the Guangzhou Science and Technology Project foundation (201510010211), and the Fundamental Research Funds for the Central Universities (Nos. 21611447 and 21613313).
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