Circulating T cells in patients with untreated acute myelogenous leukemia are heterogeneous and can be activated through the CD3/TCR complex
Circulating T cells in patients with untreated acute myelogenous leukemia are heterogeneous and can be activated through the CD3/TCR complex
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DOI：
10.1080/10245330701255163
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发表时间：
2007-01-01
期刊：
影响因子：
1.9
通讯作者：
Bruserud, Oystein
中科院分区：
文献类型：
--
作者：
Ersvaer, Elisabeth;Hampson, Peter;Bruserud, Oystein
T淋巴细胞缺陷可能导致急性髓细胞白血病（AML）中出现的免疫功能不全。因此，我们对未经治疗的AML患者的T细胞系统进行了表征。采用流式细胞仪检测45例AML患者T淋巴细胞亚群。检测了31例患者在自体AML细胞存在下，抗CD 3+抗CD 28刺激后的体外干扰素-γ（IFN-γ）释放。外周血淋巴细胞以CD 3（+）T细胞为主，CD 19（+）B细胞占淋巴细胞的比例< 10%。大多数T细胞表达α β T细胞受体（TCR α β（+）），只有少数细胞是TCR γ δ（+）。检测到CD 4（+）和CD 8（+）T细胞，CD 4：CD 8比值显示出广泛的变化，但通常> 1.0。CD 4（+）和CD 8（+）T细胞以CD 45 RA（+）细胞为主。即使在存在过量自体AML原始细胞的情况下，T细胞也可以被刺激以响应于抗-CD 3加抗-CD 28连接而释放IFNg，并且对于一个患者亚组（27个中的6个），这些IFNg水平可以通过新型蛋白激酶C（PKC）激动剂PEP 005进一步增加。总之，未经治疗的AML患者的循环T细胞主要是CD 4（+）或CD 8（+）TCR α β（+）;可以检测到CD 45 RA（+）和CD 45 R 0（+），即使在存在过量AML细胞的情况下，这些细胞也可以通过CD 3/TCR复合物活化。对于一部分患者，T细胞反应性可以通过靶向PKC进一步增加，因此这些数据表明AML患者的T细胞功能未受到抑制。
T lymphocyte defects may contribute to the immune insufficiency seen in acute myelogenous leukemia (AML). We therefore characterized the T cell system for untreated AML patients. T lymphocyte subsets were analyzed by flow cytometry for 45 AML patients. The in vitro interferon-gamma (IFN gamma) release in response to stimulation with anti-CD3 plus anti-CD28 in the presence of autologous AML cells was examined for 31 patients. The majority of circulating lymphocytes were CD3(+)T cells, and CD19(+)B cells usually constituted < 10% of the lymphocytes. Most T cells expressed the alpha beta T cell receptor (TCR alpha beta(+)), and only a minority of the cells was TCR gamma delta(+). Both CD4(+) and CD8(+)T cells were detected, the CD4: CD8 ratio showed a wide variation but was generally > 1.0. The majority of CD4(+) and CD8(+)T cells were CD45RA(+) cells. The T cells could be stimulated to release IFNg in response to anti- CD3 plus anti- CD28 ligation even in the presence of excess autologous AML blasts, and for a subset of patients (6 of 27) these IFNg levels could be further increased by the novel protein kinase C (PKC) agonist PEP005. In conclusion, circulating T cells in patients with untreated AML are mainly CD4(+) or CD8(+) TCR alpha beta(+); both CD45RA(+) and CD45R0(+) can be detected, and these cells can be activated through the CD3/TCR complex even in the presence of excess AML cells. For a subset of patients T cell responsiveness can be further increased by targeting PKC and these data therefore suggest that T cell function is not inhibited in AML patients.