Li Yangqiu, Yin Qingsong, Yang Lijian, Chen Shaohua, Geng Suxia, Wu Xiuli, Zhong Liye, Schmidt Christian A, Przybylski Grzegorz K
Institute of Hematology, Medical College, Jinan University, 510632 Guangzhou, China.
Cancer Immunol Immunother. 2009 Jul;58(7):1047-55. doi: 10.1007/s00262-008-0621-3. Epub 2008 Nov 19.
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.
Quantitative analysis of signal joint T cell recombination excision circles (deltaRec-psiJalpha 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.
The levels of deltaRec-psiJalpha 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.
The decreased numbers of universal (deltaRec-psiJalpha) 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.
T细胞免疫缺陷是癌症患者的常见特征,这可能与肿瘤的发生和发展有关。我们之前的研究表明,白血病患者中T细胞受体β可变区(TRBV)亚家族表达失衡以及T细胞克隆性扩增。在本研究中,为了进一步表征急性髓系白血病(AML)患者的T细胞免疫,我们分析了近期胸腺迁出细胞(RTE)的水平。
通过实时PCR(TaqMan)对外周血单个核细胞(PBMC)中的信号接头T细胞重组切除环(deltaRec-psiJalpha sjTRECs)进行定量分析,并通过半巢式PCR对23个TRBV-BD1 sjTRECs进行分析。本研究选取了88例AML患者;10例完全缓解的AML患者(AML-CR)和38名健康个体作为对照。
与健康个体以及完全缓解患者相比,AML患者PBMC和CD3+ T细胞中deltaRec-psiJalpha sjTRECs的水平显著降低。此外,AML患者中23个TRBV-BD1 sjTRECs的频率以及可检测到的TRBV亚家族sjTRECs的数量均显著低于健康个体。而且,AML患者中sjTRECs数量和TRBV-BD1 sjTRECs的频率随年龄呈渐进性线性下降。
通用型(deltaRec-psiJalpha)和家族特异性(TRBV-BD1)sjTRECs数量减少表明,AML患者严重的T细胞免疫缺陷与近期胸腺迁出细胞水平降低有关。在达到完全缓解的患者中,两种sjTREC计数均恢复到正常水平,表明胸腺功能恢复。更好地理解白血病患者持续免疫缺陷的潜在机制可能会带来增强免疫能力的新治疗策略。