环磷酰胺联合卡介苗对Lewis肺癌小鼠CD4~+CD25~+Treg细胞及效应细胞功能的影响

目的探讨环磷酰胺(CTX)联合卡介苗(BCG)治疗对Lewis肺癌小鼠CD4+CD25+Treg细胞和效应细胞功能的影响及CD4+CD25+Treg细胞与肿瘤的相关性。方法将传代培养的Lewis肺癌细胞接种于C57BL/6小鼠右腋皮下,建立Lewis肺癌模型。采用CTX联合BCG治疗,观察各组动物的肿瘤体积、脾脏CD4+CD25+Treg细胞数量和Foxp3 mRNA表达水平、脾脏T淋巴细胞增殖和杀伤功能。结果CTX联合BCG治疗组肿瘤生长较肿瘤组缓慢;联合治疗组小鼠脾脏CD4+CD25+Treg细胞数量明显低于肿瘤组(P<0.05);联合治疗组小鼠脾脏Foxp3 mRNA表达水平明显低于肿瘤组(P<0.05);联合治疗组小鼠脾脏T淋巴细胞增殖功能明显高于肿瘤组(P<0.05);联合治疗组小鼠脾脏CTLs细胞的杀伤活性略高于肿瘤组(P>0.05)。结论CTX联合BCG治疗可明显降低CD4+CD25+Treg细胞数量和Foxp3 mRNA表达水平,并增强机体抗肿瘤免疫应答,使肿瘤生长延缓。     

健择联合顺铂化疗对非小细胞肺癌患者外周血CD4~+CD25~+Foxp3~+调节T细胞的影响

目的探讨健择联合顺铂对非小细胞肺癌患者免疫耐受的调控作用。方法38例经病理学或细胞学确诊的NSCLC患者,采用健择、顺铂联合化疗方案,应用流式细胞仪检测化疗前后外周血CD4+CD25+Foxp3+调节T细胞(Treg)占CD4+T细胞的百分率。结果化疗前NSCLC患者外周血CD4+CD25+Foxp3+调节T细胞(Treg)占CD4+T细胞的比率明显高于健康对照组(P<0.05);化疗后NSCLC患者外周血CD4+CD25+Foxp3+调节T细胞(Treg)占CD4+T细胞的百分率较化疗前显著降低(P<0.05);但鳞癌、腺癌及腺鳞癌3组间化疗前、化疗后各项指标之间差异无统计学意义(P>0.05)。结论健择联合顺铂化疗可调控晚期非小细胞肺癌机体的肿瘤免疫耐受,改善患者的免疫功能。     

人工蛹虫草子实体对Leiws肺癌荷瘤小鼠CD4^＋CD25^＋调节性T细胞的影响

目的：观察人工蛹虫草子实体（CCM）对Lewis肺癌移植瘤生长与转移的作用,同时检测CCM对荷瘤鼠CD4^＋ CD25^＋调节性T细胞的影响,探讨其治疗肿瘤的免疫调节机制。方法：建立Lewis肺癌移植肿瘤模型。给予CCM处理后,观测肿瘤体积动态变化,计数转移灶数目,计算抑瘤率;采用流式细胞术分别于肿瘤生长第6、11、16和21d检测荷瘤鼠脾细胞CD4^＋ CD25^＋的比例;荧光定量RT—PCR检测肺转移灶组织Foxp3和TGF-β mRNA的表达水平。结果：CCM可抑制Lewis肺癌移植肿瘤的生长与转移。肿瘤生长的早期这种抑制作用比较明显,在肿瘤生长21d抑制率虽为28．6％,但治疗组肺转移灶数目明显降低,P〈0．01。与模型组相比,CCM治疗组CD4^＋CD25^＋ T细胞增高缓慢,在肿瘤生长21d时,模型组脾脏CD4^＋ CD25^＋T细胞比例为17．0％,而CCM组为13．5％,两者差异有统计学意义,P〈0．01。CCM纽肺转移灶组织Foxp3和TGF-β mRNA的表达也明显低于模型组。结论：CCM抑制肿瘤生长和转移作用可能与CCM下调荷瘤体内CD4^＋ CD25^＋ T细胞,抑制TGF-β分泌,从而激发机体的抗肿瘤免疫相关。     

非小细胞肺癌患者引流区淋巴结中CD4+CD25+调节性T细胞的检测及临床意义

目的分析非小细胞肺癌(NSCLC)患者引流区淋巴结中CD4 CD25 调节性T细胞在淋巴结局部免疫抑制状态的形成以及在肺癌发生发展中的作用。方法手术切除53例NSCLC患者引流区淋巴结,采用双标记的间接免疫荧光法检测CD4 CD25 调节性T细胞数量,实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测细胞因子TGF-β1、IL-10的表达水平,常规免疫组化方法检测CD8 T细胞的数量。结果NSCLC患者引流区转移淋巴结中,CD4 CD25 调节性T细胞(28.80%±8.06%)明显高于未转移淋巴结(15.48%±4.66%,P<0.01)。随肺癌的进展,引流区淋巴结中CD4 CD25 调节性T细胞数量增多。在转移的纵隔淋巴结(N2)和肺内淋巴结(N1)中,CD4 CD25 调节性T细胞数量分别为32.58%±7.52%和22.76%±4.67%(P<0.01)。在进展期(Ⅲ)和早期(Ⅰ Ⅱ)NSCLC患者引流区淋巴结中,CD4 CD25 调节性T细胞数量分别为30.42%±7.47%和16.22%±4.88%(P< 0.01)。NSCLC患者引流区淋巴结中的CD4 CD25 调节性T细胞数量与其自身的CD8 T细胞的数量呈负相关(r=-0.756,P<0.001)。在NSCLC患者引流区淋巴结中,CD4 CD25 调节性T细胞数量与抑制性细胞因子TGF-β1和IL-10的表达水平呈正相关(TGF-β1:r=0.645,P<0.001;IL-10:r=0.769,P<0.001)。结论NSGLC患者引流区淋巴结的CD4 CD25 调节性T细胞数量与肺癌的发展密切相关。一方面,检测肺癌患者引流区淋巴结的免疫状况为评价NSCLC患者疾病的进展程度和预后提供了一个新的免疫学指标;另一方面,在NSCLC的生物治疗中,控制CD4 CD25 调节性T细胞数量,阻断其发挥免疫抑制作用,具有广阔的临床应用前景。     

晚期非小细胞肺癌患者外周血CD4~+ CD25~+ FOXP3~+调节性T细胞的表达及临床意义

目的探讨晚期非小细胞肺癌患者外周血CD4~+ CD25~+ FOXP3~+ 调节性T(Treg)细胞的表达及其临床意义。方法采用免疫荧光术及流式细胞仪检测50例晚期非小细胞肺癌患者及50例健康对照组外周血中CD4~+ CD25~+ FOXP3~+ Treg细胞、CD4~+ CD25~+ Treg细胞、CD4~+ T细胞和CD4~+ CTLA-4~+ T细胞的表达。结果晚期非小细胞肺癌患者外周血中CD4~+ CD25~+ FOXP3~+ Treg细胞、CD4~+ CD25~+ Treg细胞和CD4~+ CTLA-4~+ T细胞的比例均高于健康对照组(均P<0.05),CD4~+ T细胞的比例均低于健康对照组(均P<0.05)。结论晚期非小细胞肺癌患者外周血CD4~+ CD25~+ FOXP3~+ Treg细胞比例高于健康对照者,可能与肺癌患者的免疫抑制和肿瘤进展相关。     

非小细胞肺癌患者外周血CD4＋CD25＋Foxp3＋调节性T细胞检测及临床意义

[目的]探讨非小细胞肺癌患者外周血CD4＋CD25＋Foxp3＋调节性T细胞（Treg）表达及临床意义。[方法]流式细胞术检测30例非小细胞肺癌组患者及12例健康志愿者外周血CD4＋CD25＋Foxp3＋Treg百分比。[结果]肺癌组外周血CD4＋CD25＋Foxp3＋细胞百分比（6.24%±2.01%）高于健康对照组（4.83%±0.85%）（P〈0.05）,外周血CD4＋CD25＋Foxp3＋细胞百分比在肺癌患者不同性别、年龄、病理、KPS及肿瘤标志物正常与否之间比较无差异（P〉0.05）,Ⅳ期患者表达高于Ⅰ～Ⅲ期患者（P〈0.05）,带瘤患者表达高于无瘤患者（P〈0.05）,有气虚证、血瘀证患者高于无气虚证、血瘀证患者（P〈0.05）。[结论]检测肺癌患者外周血CD4＋CD25＋Foxp3＋Treg表达在了解患者肿瘤进展情况和机体免疫功能状态方面有一定价值,其表达升高与患者出现气虚证和血瘀证有关。     

DC-CIK对胃癌合并腹水患者外周血CD4+CD25+调节性T细胞增殖及功能的影响

目的:探讨DC-CIK对胃癌合并腹水患者外周血CD4+CD25+调节性T胞(Treg细胞)比例及功能的影响。方法:60例胃癌合并腹水患者,于输注DC-CIK前1天及DC-CIK治疗结束后1周分别采集外周血。流式细胞术检测外周血Treg细胞的比例,RT-PCR法检测其Foxp3mRNA表达情况;将分选出的Treg细胞和CD4+CD25-T细胞分为单纯Treg细胞组（A组）、1∶1混合培养（B组）、单纯CD4+CD25-细胞组（C组）进行培养,3H-TdR掺入法检测Treg细胞抑制CD4+CD25-细胞增殖的能力。结果:治疗后外周血Treg细胞占CD4+T细胞的比例较疗前显著下降［(6.21±1.37)% vs (9.38±1.06)%,P＜0.05］。治疗后Treg细胞Foxp3mRNA表达水平较治疗前显著下降［(56.18±13.25)% vs (85.26±11.58)%,P＜0.05］。治疗后Treg对CD4+CD25-T细胞抑制增殖能力较治疗前明显下降［(37.31±4.16)% vs (48.92±5.25)%,P＜0.05］。结论:输注DC-CIK免疫治疗,可显著降低胃癌合并腹水患者外周血Treg细胞比例,下调Foxp3mRNA表达水平,降低Treg细胞免疫抑制功能,有利于诱导抗肿瘤免疫效应。     

鼻咽癌组织与外周血CD4+CD25+调节性T细胞检测及临床意义

目的 通过检测鼻咽癌患者肿瘤组织及外周血中CD4+T、CD8+T、CD4+CD25T、CD4+CD25+T细胞的频数,寻找客观、全面评价鼻咽癌患者免疫状态的临床指标.方法 采用流式细胞术检测40例初诊鼻咽癌患者及10例正常时照鼻咽部组织和外周血CD4+T、CD8+T、CD4+CD25-T、CD4+CD25+T细胞比例.结果 鼻咽癌患者CD4+T细胞比例及CD4+/CD8+T比值均低于对照组(P<0.05),而CD8+T细胞两组间差异无统计学意义(P>0.05),但是CD4+/CD8+T比值在鼻咽癌组织与外周血间差异无统计学意义(P>0.05).鼻咽癌组织及外周血中CD4+CD25+T细胞比例都高于对照组(P<0.05),同时癌组织中该细胞比例远远高于外周血(P<0.05).在鼻咽癌组织中CD4+CD25+T细胞与CD8+T细胞、CD4+CDQ5-T细胞呈负相关(r分别为-0.70、-0.675,P<0.05),而在外周血中没有相关关系(P>0.05).在不同T(原发肿瘤大小)组间,T4组的鼻咽癌组织中CD4+CD25+T细胞分别高于T1、T2、T3各组(P<0.05).而在T1、T2、T3各组间差异无统计学意义(P>0.05);鼻咽癌中CD4+CD25+T细胞比例与患者有无淋巴结转移并无关系(P>0.05);鼻咽癌组织中Ⅲ+Ⅳ期组CD4+CD25+T细胞比例高于Ⅰ+Ⅱ期组(P<0.05),而在外周血中两组间差异无统计学意义(P>0.05).结论 CD4+CD25+T细胞与鼻咽癌病程进展无相关性,但是联合检测患者肿瘤组织及外周血中CD4+CD25+T细胞的频数并结合既往CD4+/CD8+T比值会全面反应患者免疫状态,为临床治疗提供依据.     

CD+4CD+25Foxp+3调节性T细胞在T细胞非霍奇金淋巴瘤中的研究进展

 CD+4 CD+25 调节性T细胞（CD+4 CD+25 Treg）是一个具有独特免疫调节功能的T细胞亚群, 天然的CD+4 CD+25 Treg起源于胸腺,获得性CD+4 CD+25 Treg可在外周由CD+4 CD-25 T细胞诱导产生,其分子表面表达特异性的转录抑制因子Foxp3,又可表达CD4、CD25、CTLA-4 （CD152） 、GITR等膜分子,主要功能具有免疫抑制性和免疫无能性。近年来研究发现,其在非霍奇金淋巴瘤（NHL）中存在表达异常,某些NHL外周血中或瘤内均存在CD+4 CD+25 Treg表达升高,且有研究表明其表达量随肿瘤增长和分期而增加。增加的CD+4 CD+25 Treg可加速肿瘤生长及再发,且可抑制自身效应性T细胞（CD+4 T／CD+8 T）功能,在肿瘤免疫逃逸机制中发挥一定作用。文章就CD+4 CD+25 Foxp3+调节性T细胞在T细胞非霍奇金淋巴瘤（T-NHL）（主要为皮肤T细胞淋巴瘤及成年人T细胞淋巴瘤）中的研究进展进行综述。     

胃癌患者外周血CD4+CD25+调节性T细胞的检测及其临床意义

目的探讨胃癌患者外周血CD4 CD25 调节性T细胞水平的特点及其临床意义。方法采用流式细胞术检测35例胃癌患者外周血CD4 CD25 调节性T细胞水平并进行分层分析。结果健康对照组CD4 CD25 调节性T细胞水平为(8.69±2.28)%,35例胃癌患者CD4 CD25 调节性T细胞比例为(17.77±8.45)%,统计学有显著差异(P<0.01);进一步分层分析显示随疾病进展外周血CD4 CD25 调节性T细胞水平升高,在III期、IV期尤为明显,统计学有极显著差异(P<0.01)。结论胃癌患者外周血CD4 CD25 调节性T细胞水平的升高与胃癌免疫功能低下及肿瘤的发生发展密切相关,去除这群细胞可有效诱导肿瘤免疫,为肿瘤治疗提供一种新的方法。     

淋巴瘤细胞EL-4培养上清液对CD4＋CD25＋调节性T细胞比例的调节作用

目的探讨肿瘤细胞是否能上调CD4＋CD25＋调节性T细胞（Treg细胞）的比例。方法将小鼠淋巴瘤细胞株EL4培养上清液与正常小鼠脾脏淋巴细胞混合培养72h,流式细胞仪检测其中CD4＋CD25＋Treg细胞含量,RT—PCR检测Foxp3mRNA的表达,实验重复3次。结果和EL-4培养上清液混合培养的正常小鼠脾脏淋巴细胞中CD4＋CD25＋Treg细胞的比例高于对照组（P〈0．05）,在CD3单抗刺激的同时加入EL-4培养上清液后,小鼠脾脏中CD4＋CD25＋Treg细胞仍呈同步增加（P〈0．05）;且Foxp3mRNA的表达增加。结论淋巴瘤细胞分泌的免疫调节因子能诱导CD4＋CD25＋Treg细胞的增生,提示肿瘤可以上调CD4＋CD25＋Treg细胞比例。     

CD4+CD25+CCR6+调节性T细胞在小鼠乳腺癌模型中对CD8+T细胞的抑制作用

目的：观察CD4+CD25+CCR6+调节性T细胞（简称CCR6+Tregs）体内对CD8+T细胞功能的抑制作用,并探讨其与肿瘤免疫逃逸的关系。方法：建立4T1乳腺癌细胞荷瘤裸鼠模型,FACS分选CCR6+Tregs,检测其Foxp3的表达;FACS分选4T1特异性CD8+T细胞,CFSE标记后分别与CCR6+Tregs或CCR6Tregs共同过继转输入4T1荷瘤裸鼠体内,观察荷瘤裸鼠肿瘤生长情况和小鼠存活时间;FACS检测肿瘤组织中CD8+T细胞的增殖、细胞因子IFNγ的产生和颗粒酶B的表达情况。结果：CCR6+Tregs和CCR6Tregs均高表达Foxp3;CCR6+Tregs和CD8+T细胞共转输组4T1荷瘤裸鼠肿瘤的生长明显快于CCR6Tregs共转输组和CD8+T细胞单转输组,同时该组荷瘤裸鼠生存时间也明显缩短（P<0.05）;CCR6+Tregs和CD8+T细胞共转输组CD8+T细胞的增殖、IFNγ的产生和颗粒酶B的表达均明显低于CCR6Tregs共转输组和CD8+T细胞单转输组（P<0.05）。结论：CCR6+Tregs在体内可以有效抑制CD8+T细胞的功能,其在肿瘤免疫逃逸和肿瘤发生、发展中发挥重要作用。     

Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent

The CD25- and CD25+ CD4 T-lymphocyte compartments are tightly regulated. We show here that tumors break such balance, increasing the number of CD4+CD25+ T cells in draining lymph node and spleen but not contralateral node of tumor-bearing mice. Tumor injection in thymectomized and CD25-depleted mice shows that CD4+CD25+ T-cell expansion occurs even in the absence of the thymus and independently from proliferation of preexisting CD25+ T cells. These newly generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3 expression and suppression of CD3-stimulated or allogeneic effector cell proliferation. Transfer of congenic Thy1.1 CD4+CD25- T cells, from mice treated or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of recovered donor lymphocytes indicate that conversion is the main mechanism for acquiring the expression of CD25 and Foxp3 through a process that does not require proliferation. Although conversion of CD4+CD25- T cells for generation of T regs has been described as a natural process that maintains peripheral T-reg population, this process is used by the tumor for immune escape. The prompt recovery of T regs from monoclonal antibody-mediated CD25 depletion in tumor-bearing mice suggests attempts able to inactivate rather than deplete them when treating existing tumors.     

Functional and phenotypic characteristics of CD4+CD25highFoxp3+ Treg clones obtained from peripheral blood of patients with cancer

Circulating human CD4(+)CD25(high)Foxp3(+) T cell populations (Treg) may contain activated CD4(+)CD25(+) T cells interfering with Treg evaluation. To gain insights into the phenotypic and functional characteristics of Treg in patients with cancer, we have analyzed CD4(+)CD25(high) populations at the clonal level. Single-cell sorted (SCS) CD4(+)CD25(high) T cells obtained from PBMC of normal controls (NC) or patients with squamous cell carcinoma of the head and neck (HNSCC) were plated at 1 cell/well in 96 well plates and expanded with anti-CD3/anti-CD28 Abs and 1,000 IU IL-2/mL in the presence or absence of rapamycin (1 nM). All generated clones were evaluated for the phenotype by flow cyometry and suppressor function in CFSE-based proliferation assays. Clones had heterogeneous CD25 expression levels. Cloning efficiency of CD4(+)CD25(high) T cells was low. CD25(high) clones expressed CTLA-4, Foxp3, CD62L, but little GITR and suppressed proliferation of autologous CD4(+)CD25(-) responder cells. Clones of activated CD4(+)CD25(interm./low) cells expressed intermediate to high levels of GITR and HLA-DR and did not suppress proliferation of responder cells. The number, suppressor phenotype and function of CD25(high) Treg clones were significantly enhanced in HNSCC patients relative to NC (p 相似文献   

Increased Frequency of Foxp3+ Regulatory T Cells in Mice with Hepatocellular Carcinoma

The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Tregcells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases,transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumourimmunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigatewhether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model wasestablished to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flowcytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzedby immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+spleen lymphocytes of tumor bearing mice (18.8%±1.26%) was found to be significantly higher than that innormal mice (9.99%±1.90%) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there wasan increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumorinfiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed,and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellularcarcinoma mice and the Treg may be a promising therapeutic target for cancer.     

Low-dose photon and simulated solar particle event proton effects on Foxp3+ T regulatory cells and other leukocytes

Radiation is a major factor in the spaceflight environment that has carcinogenic potential. Astronauts on missions are continuously exposed to low-dose/low-dose-rate (LDR) radiation and may receive relatively high doses during a solar particle event (SPE) that consists primarily of protons. However, there are very few reports in which LDR photons were combined with protons. In this study, C57BL/6 mice were exposed to 1.7 Gy simulated SPE (sSPE) protons over 36 h, both with and without pre-exposure to 0.01 Gray (Gy) LDR g-rays at 0.018 cGy/h. Apoptosis in skin samples was determined by immunohistochemistry immediately post-irradiation (day 0). Spleen mass relative to body mass, white blood cells (WBC), major leukocyte populations, lymphocyte subsets (T, Th, Tc, B, NK), and CD4(+)CD25(+)Foxp3+ T regulatory (Treg) cells were analyzed on days 4 and 21. Apoptosis in skin samples was evident in all irradiated groups; the LDR+sSPE mice had the greatest expression of activated caspase-3. On day 4 post-irradiation, the sSPE and LDR+sSPE groups had significantly lower WBC counts in blood and spleen compared to non-irradiated controls (p < 0.05 vs. 0 Gy). CD4(+)CD25(+)Foxp3(+) Treg cell numbers in spleen were decreased at day 4, but proportions were increased in the sSPE and LDR+sSPE groups (p < 0.05 vs. 0 Gy). By day 21, lymphocyte counts were still low in blood from the LDR+sSPE mice, especially due to reductions in B, NK, and CD8(+) T cytotoxic cells. The data demonstrate, for the first time, that pre-exposure to LDR photons did not protect against the adverse effects of radiation mimicking a large solar storm. The increased proportion of immunosuppressive CD4+CD25(+) Foxp3(+) Treg and persistent reduction in circulating lymphocytes may adversely impact immune defenses that include removal of sub-lethally damaged cells with carcinogenic potential, at least for a period of time post-irradiation.     

Adult T-cell leukemia/lymphoma cells from blood and skin tumors express cytotoxic T lymphocyte-associated antigen-4 and Foxp3 but lack suppressor activity toward autologous CD8+ T cells

Adult T cell leukemia/lymphoma (ATL) cells share the CD4⁺CD25⁺ phenotype with regulatory T (Treg) cells. However, it is still controversial whether ATL cells are Treg cells. The aim of the present study was to investigate the Treg nature of ATL cells obtained from peripheral blood and skin tumors in terms of their phenotype and function. By flow cytometry and immunohistochemistry, the expression of the Treg-associated molecule cytotoxic T lymphocyte-associated antigen (CTLA)-4 and Foxp3 was examined in freshly isolated circulating and skin-infiltrating tumor cells from 21 ATL patients with skin eruptions. The expression of CTLA-4 on freshly isolated circulating tumor cells was elevated in two of 15 patients, and Foxp3 was expressed intracytoplasmically at high levels in three of nine patients. In five of the patients examined, skin-infiltrating tumor cells bore variously elevated CTLA-4 with high Foxp3 expression. The potentiality of ATL cells as Treg cells was further addressed by stimulating ATL cells with anti-CD3/CD28 monoclonal antibodies and monitoring CTLA-4 expression. With the stimulation, even CTLA-4-low ATL cells expressed higher levels of CTLA-4 than normal CD4⁺CD25⁺ cells. To study function, ATL cells isolated from blood and skin tumors were tested for their ability to suppress the proliferation of autologous CD8⁺ T cells stimulated with allogeneic lymphocytes. Despite the expression of CTLA-4 and Foxp3, these tumors were incapable of suppressing the proliferation of autologous CD8⁺ T cells. ATL cells are phenotypically Treg cells in at least some patients, but lack immunoregulatory functions, at least toward CD8⁺ T cells. ( Cancer Sci 2008; 99: 98–106)     

食管癌患者化疗前后ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞及Ｆｏｘｐ３ｍＲＮＡ的表达及其临床意义

目的：探讨晚期食管癌患者化疗前后外周血中ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞及Ｆｏｘｐ３ｍＲＮＡ的表达变化及其临床意义。方法：采用流式细胞术检测６８例晚期食管癌患者化疗前后外周血ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞的水平,并与４０例健康成人进行比较。同时运用ＲＴ-ＰＣＲ方法检测其中４０例患者化疗前后外周血调节性Ｔ细胞Ｆｏｘｐ３基因ｍＲＮＡ的表达情况。结果：（１）食管癌患者外周血中ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞占ＣＤ４＋Ｔ细胞总数的（１.８２±０.５４）％,显著高于健康对照组的（１.５２±０.７０）％（Ｐ＜０.０１）;（２）化疗前患者外周血中ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞为（１.８２±０.５４）％,明显高于化疗后的（１.６６±０.５８）％（Ｐ＜０.０5）;（３）化疗前患者调节性Ｔ细胞Ｆｏｘｐ３基因ｍＲＮＡ的相对表达量为０.３１８±０.０２７,明显高于化疗后的０.２６６±０.０２８（Ｐ＜０.０５）。结论：食管癌患者接受化疗后外周血中Ｆｏｘｐ３ｍＲＮＡ水平与ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞数量表达均显著下降,推测Ｆｏｘｐ３基因可能对ＣＤ４＋ＣＤ２５ｈｉｇｈＴ细胞有重要的调节功能,从而影响食管癌患者化疗后ＣＤ４＋ＣＤ２５ｈｉｇｈ调节性Ｔ细胞的水平。