In:
Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4971-4971
Abstract:
T-cell immunodeficiency is a common feature in patients with leukemia, lower activation of T cells was one of reasons. The TCR zeta chain has emerged as a key subunit of the T-cell antigen receptor, which plays a central role in the signal-transducing events leading to T cell activation. The proliferation and activation of T cells may be inducted by T cell related cytokines. In this study, we explored the change of TCR zeta gene expression and the clonality of T cells after induction with different immune cytokines, including IL-2, IL-7 or IL-12. CD3+ T cells sorted from peripheral blood of 4 cases with AML were induced with different immune cytokines, including IL-2, IL-7, IL-12, anti-CD3 and anti-CD28 antibodies in vitro. The expression levels of TCR zeta gene and related genes in T cells before and after induction were then analyzed by fluorescence quantitative RT-PCR. The distribution and clonality of TCR Vβ subfamily T cells were analyzed by RT-PCR and Genescan techniques. Increasing expression levels of TCR zeta gene and zap-70 (TCR zeta chain associated-protein) gene in CD3+T cells from AML patients were found after induction with single stimulating factor or the combination with different cytokines, while the expression of FcεRIγ (TCR ζ gene complementary factor) was down-regulated. We further compared the T cell clonality in CD3+T cells from AML patients after cytokine induction, eight to 22 TCR V β subfamilies could be detected in T cells from AML cases, most of them displayed polyclonal expansion. The number of expressed TCR Vβ subfamilies was increased without the change of clonality in T cells induced by CD3+CD28+IL7. In conclusion, TCR zeta gene and its related genes could be upregulated through induction with different cytokine combination such as IL-2, IL-7 and IL-12, therefore to improve the T cell activation in patients with AML. And the main effect of cytokines might to maintain the T cell clonality and nonspecific amplification of T cell clones. Further investigation can be designed to amplify the specific anti-AML TCR Vβ clones using AML associated antigens and such cytokine combination. Disclosures Shi: National Natural Science Foundation of China (no. 81100353, 81270604), the Fundamental Research Funds for the Central Universities (No. 21611447, 21612116), And Medical Science Foundation of Guangdong Province(A2011325). : Research Funding.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V124.21.4971.4971
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2014
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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