Abstract
Background
T cell immunodeficiency is a common feature in cancer patients, which may relate to initiation and development of tumor. Our previous study showed skewed expression of T cell receptor beta variable region (TRBV) subfamilies and clonal expansion of T cells in leukemia patients. In the present study, in order to further characterize the T cell immunity in acute myeloid leukemia (AML) patients, the level of recent thymic emigrants (RTE) was analyzed.
Materials and methods
Quantitative analysis of signal joint T cell recombination excision circles (δRec-ψJα sjTRECs) was performed in peripheral blood mononuclear cells (PBMCs) by real-time PCR (TaqMan), and the analysis of 23 TRBV-BD1 sjTRECs was performed by semi-nested PCR. Eighty-eight cases with AML were selected for this study; ten AML cases in complete remission (AML-CR) and 38 healthy individuals served as controls.
Results
The levels of δRec-ψJα sjTRECs in PBMCs and CD3+ T cells were significantly decreased in AML patients, compared with healthy individuals and in patients in completive remission. Also the frequency of 23 TRBV-BD1 sjTRECs, and the number of detectable TRBV subfamily sjTRECs were significantly lower in AML patients than in healthy individuals. Moreover, the sjTRECs numbers and the frequency of TRBV-BD1 sjTRECs showed a progressive linear decline with age in AML patients.
Conclusions
The decreased numbers of universal (δRec-ψJα) and family-specific (TRBV-BD1) sjTRECs indicate that the severe T cell immunodeficiency in AML patients is associated with reduced levels of recent thymic emigrants. In patients achieving complete remission both sjTREC counts return to normal values indicating the recovery of thymic function. Better understanding of the mechanisms underlying persistent immunodeficiency in leukemia patients may lead to novel treatment strategies to enhance immune competence.
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Acknowledgments
This project was sponsored by grants from National Natural Science Foundation of China (No. 30270579), Natural Science Foundation of Guangdong Province (No.23001) and the Department of Education of Guangdong Province (No. Q 02022). We thank Prof. Xin Du from Dept. of Hematology, Guangdong Provincial People’s Hospital for kindly providing AML samples.
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Li, Y., Yin, Q., Yang, L. et al. Reduced levels of recent thymic emigrants in acute myeloid leukemia patients. Cancer Immunol Immunother 58, 1047–1055 (2009). https://doi.org/10.1007/s00262-008-0621-3
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DOI: https://doi.org/10.1007/s00262-008-0621-3