靶向抗前列腺癌药物的研究新进展*

前列腺癌在男性癌症死亡率中仅次于肺癌,占第二位。前列腺癌细胞特异性地分泌大量的前列腺特异性抗原(PSA)、人腺激肽释放酶2(hK2)和前列腺特异性膜抗原(PSMA),设计合成被PSA,hK2和PSMA水解活化的前药,可以针对前列腺癌进行靶向治疗。前药的结构是PSA,hK2和PSMA特异性寡肽和抗肿瘤药物的偶连物,作用原理是前药在血浆中没有活性,在瘤组织中多肽链被PSA、hK2或PSMA水解释放抗肿瘤药物,杀伤癌细胞。前药既降低了抗肿瘤药物的毒副作用,又提高了治疗指数。现从结构、血浆稳定性、靶向性、细胞试验、动物实验等方面系统地总结了前药的研究进展。     

食管癌抗原和超抗原构建肿瘤疫苗的抗癌作用研究

目的利用食管癌肿瘤可溶性抗原(TSA)和超抗原(SEC)构建肿瘤疫苗,刺激外周血淋巴细胞,诱导产生细胞毒性T细胞(CTLs),对肿瘤细胞进行体内外杀伤作用研究,以探讨其抗肿瘤作用。方法外周血淋巴细胞经肿瘤疫苗作用,进行体外培养,诱导产生细胞毒性T细胞;细胞毒实验测定效应细胞杀伤活性;建立小鼠移植瘤模型,用肿瘤疫苗进行干预治疗,观察其治疗效果。结果经肿瘤疫苗刺激的淋巴细胞组诱导的CTLs对靶细胞杀伤活性显著高于单纯淋巴细胞组(P<0.05),对TSA来源的食管癌细胞具有选择性杀伤作用;体内研究发现肿瘤疫苗能显著减轻小鼠荷瘤负担,延长生存期。结论肿瘤可溶性抗原与超抗原SEC构建的肿瘤疫苗能产生高效特异性的抗肿瘤效果,显示出良好的抗肿瘤免疫治疗作用。     

热休克蛋白抗原肽致敏的脐血树突状细胞治疗肺癌的实验研究

目的研究热休克蛋白抗原肽致敏的脐血树突状细胞体外对肺癌细胞的杀伤作用。方法用体外构建的热休克蛋白-抗原肽复合物刺激经组合细胞因子诱导的脐血树突状细胞,MTT法检测其对肿瘤细胞的杀伤作用。结果所得蛋白经电泳及Western blot进行蛋白分子量及性质鉴定为热休克蛋70。热休克蛋白-抗原肽负载可以促进脐血树突状细胞对T细胞的激发作用,使其对靶细胞有了更强的生长抑制作用。各组T细胞杀伤活性分别为:负载抗原组(85.77±1.03)%(正常T细胞)、(45.01±1.66)%(肺癌患者T细胞);未负载抗原组(41.92±1.38)%(正常T细胞)、(13.99±3.07)%(肺癌患者T细胞)。组间比较差异有统计学意义(P<0.01)。结论热休克蛋白抗原肽负载脐血树突状细胞能有效激发外周血T淋巴细胞,使其对靶细胞有了更强的生长抑制作用。本研究为解决树突状细胞的来源及开发特异性CTL的治疗开创了条件。     

血清前列腺特异抗原对前列腺癌的诊断评价

目的对血清前列腺特异抗原(PSA)和前列腺特异抗原密度(PSAD)对前列腺癌的诊断价值进行分析评价。方法使用化学发光免疫分析法对56例前列腺增生患者与33例前列腺癌患者的血清前列腺特异抗原(PSA)进行测定并计算出前列腺特异抗原密度(PSAD)值,对两组得出数据进行分析比较。结果前列腺癌患者的血清前列腺特异抗原(PSA)、前列腺特异抗原密度(PSAD)显著高于前列腺增生组,当以PSA>4.0ng/mL,PSAD>0.20为临界值时,能够显著提高前列腺癌诊断的特异性。结论血清前列腺特异抗原(PSA)单项检测对前列腺癌进行诊断是较为敏感的指标,联合测定前列腺特异抗原密度(PSAD)能够明显提高前列腺癌诊断的特异性与准确度,便于与前列腺增生的鉴别诊断。     

超抗原金黄色葡萄球菌肠毒素C和肿瘤可溶性抗原诱导的细胞毒性T淋巴细胞的杀瘤效应

目的 探讨肿瘤可溶性抗原(TSA)联合超抗原金黄色葡萄球菌肠毒素C(SEC)诱导的细胞毒性T淋巴细胞(CTLs)对肿瘤细胞的杀伤作用.方法 实验分为对照组(淋巴细胞)和实验组(SEC+ TSA+淋巴细胞).分离肿瘤患者外周血淋巴细胞,经TSA、超抗原SEC联合作用诱导产生CTLs,对其增殖、细胞表型、杀瘤活性进行观察和测定.结果 经TSA、SEC联合刺激的淋巴细胞组增殖活性明显增强.实验组和对照组CD3均阳性表达,实验组CD8+明显高于对照组(49.07％比27.52％,P＜0.05).经肺癌TSA、超抗原SEC联合刺激淋巴细胞组培养诱导的CTLs,当效靶比为20∶1时对CALU-6、自体肺癌细胞、Hela细胞杀伤活性明显高于效靶比为10∶1[分别(89.6±3.7)％比(51.5±4.0)％,(92.0±4.0)％比(54.5±4.0)％,(65.0±3.8)％比(35.3±2.4)％,均P＜0.05];效应细胞对人肺癌细胞株CALU-6、自体肺癌细胞的杀伤活性明显高于Hela细胞(P＜0.05).结论 经肿瘤抗原和超抗原SEC诱导的CTL能够产生高效特异性的杀瘤效应.     

多表位BCR—ABL融合抗原体外诱导对白血病原代细胞的特异性杀伤

目的 体外观察多表位BCR—ABL融合抗原诱导对白血病细胞的特异性杀伤效应，探索慢性髓细胞性白血病(chronic myeloid leukemia，CML)免疫治疗新途径。方法从外周血单个核细胞培养DC，以BCR—ABL融合抗原脉冲刺激DC，诱导特异性CTL产生；MTT法检测CTL对白血病靶细胞的特异性杀伤活性。结果 融合抗原刺激产生的CTL能特异性杀灭含BCR—ABL融合基因的白血病靶细胞。结论 我们所设计表达的多表位BCR—ABL融合抗原能在体外诱导特异性抗白血病免疫反应，对白血病细胞产生特异性杀伤，为进一步的体内的实验奠定了基础。     

食管癌可溶性抗原和超抗原构建肿瘤疫苗的免疫活性成分分析

目的对食管癌可溶性抗原和超抗原SEC构建的肿瘤疫苗中的免疫活性成分进行分析,从而为探讨其抗癌机制打下理论基础。方法提取食管癌抗原,和超抗原SEC构建成肿瘤疫苗;分离人外周血单个核细胞（peripheral blood mononuclear cells,PBMC）,经肿瘤疫苗联合作用,进行体外培养,观察其增殖活性;流式细胞术FCM和细胞毒试验测定效应细胞表型和杀伤活性;提取食管癌细胞中的细胞膜抗原（mAg）、热休克蛋白70（HSP70）、DNA、RNA和细胞内多肽（Peptides）,用于诱导PBMC增殖,培养6d,用3H-Tdr掺入法测定细胞增值,确定其有效成分。结果经肿瘤疫苗刺激的PBMC组增殖活性最强,于72h达到高峰,并且特异性刺激CD8＋T细胞群增值。肿瘤疫苗刺激的PBMC组诱导的CTLs对靶细胞杀伤活性显著高于单纯PBMC组（P〈0.01）。食管癌细胞中的膜抗原和细胞内多肽能显著刺激PBMC增殖。结论食管癌抗原与超抗原构建的肿瘤疫苗能诱导效应细胞明显增殖、活化、并产生高效、特异的抗肿瘤效果,具有免疫活性的成分是细胞中的mAg和细胞内多肽。     

IFN-γ联合DC疫苗对口腔鳞癌细胞的抑制作用

目的 观察干扰素γ(IFN-γ)与树突状细胞(DC)疫苗联合使用后对口腔鳞癌的抑制作用.方法 采用RT-PCR方法 分析抗原提呈相关基因Tap1和Tapasin在人正常口腔黏膜细胞以及口腔鳞癌细胞系中的表达.采用IFN-γ处理口腔鳞癌细胞系CAL27后,分别在mRNA和蛋白水平检测Tap1和Tapasin的变化.将处理后的肿瘤细胞提取冻融抗原后致敏DC,并将其与同源的T淋巴细胞共培养,诱导出抗原特异性的细胞毒T细胞(CTL),在体外对口腔鳞癌细胞进行杀伤试验.结果 与正常人口腔黏膜上皮细胞相比,肿瘤细胞中Tap1和Tapasin的表达明显降低(均在50%以下).使用IFN-γ处理后,其在mRNA和蛋白水平的表达均明显提高.CTL行体外杀伤实验时发现,IFN-γ处理组肿瘤杀伤效率明显提高,A组(IFN-γ处理48 h)的肿瘤细胞杀伤率达到(87.21±4.67)%,而B组(IFN-γ处理24 h)及C组(IFN-γ处理0 h)则分别达到(73.34±4.52)%和(54.68±4.21)%(P<0.01).结论 口腔鳞癌细胞中抗原提呈相关基因Tap1和Tapasin的表达明显降低,使用IFN-γ处理后可明显提高其表达.将处理后的肿瘤细胞提取抗原后,诱导出抗原特异性CTL,可显著提高其肿瘤杀伤率.     

负载肝癌排斥抗原肽的树突状细胞瘤苗活化T细胞的应用

目的　探讨负载肝癌排斥抗原肽SLIVHLNEV(C met突变肽 ) [1 ] 的树突状细胞瘤苗活化的T细胞在体外及裸鼠肝癌模型体内诱导的特异性抗肿瘤免疫。方法　用肝癌排斥抗原肽SLIVHLNEV致敏从脾脏中分离培养的树突状细胞 ,再与同源T淋巴细胞混合培养。乳酸脱氢酶 (LDH)释放法检测细胞毒作用。同时建立荷人肝癌细胞系HHCC的裸鼠移植瘤模型 ,观察DC瘤苗活化的T细胞预防移植瘤发生和抑制移植瘤生长的作用。结果　在体外实验中 ,DC瘤苗诱导的CTLs能够特异性杀伤HHCC肝癌细胞。在裸鼠模型中 ,CTLs不但能预防裸鼠移植瘤的发生 ,而且抑制裸鼠移植瘤生长。结论　负载肝癌排斥抗原肽SLIVHLNEV的树突状细胞瘤苗活化的T细胞在体外和裸鼠模型中均可诱导较强的抗肿瘤免疫     

热休克蛋白gp96-肽复合物体外对人肝癌细胞的抗肿瘤效应

目的研究热休克蛋白gp96-肽复合物修饰树突状细胞(DC)后对人肝癌细胞的体外特异抗肿瘤效应。方法从人原发性肝癌组织中提取gp96-肽复合物,用其修饰DC细胞后与T淋巴细胞共同培养,以MTT法检测该复合物介导的细胞毒性T细胞(CTL)对不同来源人肝癌细胞的抗肿瘤效应,并与粗提抗原修饰DC细胞组相比较。结果 gp96-肽复合物诱导的CTL对原代肝癌细胞杀伤效率为74.3%,明显高于粗提抗原组(42.5%)和未加抗原组(14.4%)(P<0.01),粗提抗原组对肝癌细胞杀伤效率高于未加抗原组(P<0.01)。且该复合物的抗肿瘤效应具有一定的组织特异性。结论 gp96-肽复合物修饰的DC细胞,在体外能刺激产生特异的抗肿瘤细胞毒性T细胞,因而热休克蛋白gp96在肿瘤免疫治疗中具有重要的实用价值。     

抗CD40抗体增强宫颈癌肽疫苗的治疗作用

目的：探讨抗CD40抗体对宫颈癌肽疫苗治疗作用的影响。方法将乳头状病毒结构性蛋白 E7表位肽（ E749－57,H－2Db限制性,CD8 T细胞表位）与Toll样受体7配体（Gardiquimod）组成疫苗,C57BL／6小鼠给予疫苗及抗CD40抗体免疫后取得外周血及脾组织CD8 T细胞,利用流式细胞仪分析特异性CD8 T细胞数量,Elisa检测CD8 T细胞与TC－1细胞（表达HPV E7蛋白的小鼠宫颈癌细胞）共孵育后干扰素（ INF－γ）表达水平。另取15只皮下荷瘤小鼠,监测免疫后肿瘤生长速度。结果与单用疫苗组相比,抗 CD40抗体明显增加小鼠外周血肿瘤特异性 CD8 T细胞数量（16．50±0．8185％ vs 9．747±1．834％,P＝0．0282）,且内源性CD8 T细胞体外与TC－1细胞共孵育可以分泌INF－γ,体内显著抑制皮下肿瘤生长（ P＜0．001）。结论抗CD40抗体增强肽疫苗诱发的免疫应答,有潜力成为一种良好的佐剂。     

外阴硬化性苔藓患者HLA-DR抗原的表达及T细胞亚群变化的研究

目的研究外阴硬化性苔藓患者病变组织中的HLA-DR抗原表达和外周血中T细胞亚群水平的变化,探讨上述因素在其发病中的作用机制。方法应用免疫组化SP法检测30例患者（研究组）及21例其他良性病变患者（对照组）外阴组织HLA-DR抗原的表达情况;另用流式细胞术检测研究组和对照组血清中CD3＋、CD4＋、CD8＋及CD4＋/CD8＋的水平,并进行比较。结果①研究组外阴病变组织中HLA-DR抗原阳性表达率为30%,显著高于对照组正常外阴组织中HLA-DR抗原表达率（4.77%）,差异有统计学意义（P〈0.05）。②研究组血清中CD3＋、CD4＋的水平略低于对照组,CD8＋的水平略高于对照组,差异均无统计学意义（P〉0.05）。③研究组血清CD4＋/CD8＋的比值1.23±0.26,显著低于对照组CD4＋/CD8＋的比值（1.55±0.62）,差异有统计学意义（P〈0.05）。结论以HLA-DR为代表的遗传免疫因素可能与本病患者免疫功能紊乱,导致免疫应答过度,造成机体自身组织的损伤有关。     

A novel cyclic peptide targeting LAG-3 for cancer immunotherapy by activating antigen-specific CD8+ T cell responses

PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy. However, many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation. The combination of checkpoint blockers has been proposed to increase the response rates. Besides, antibody drugs have disadvantages such as inclined to cause immune-related adverse events and infiltration problems. In this study, we developed a cyclic peptide C25 by using Ph.D.-C7C phage display technology targeting LAG-3. As a result, C25 showed a relative high affinity with human LAG-3 protein and could effectively interfere the binding between LAG-3 and HLA-DR (MHC-II). Additionally, C25 could significantly stimulate CD8⁺ T cell activation in human PBMCs. The results also demonstrated that C25 could inhibit tumor growth of CT26, B16 and B16-OVA bearing mice, and the infiltration of CD8⁺ T cells was significantly increased while FOXP3⁺ Tregs significantly decreased in the tumor site. Furthermore, the secretion of IFN-γ by CD8⁺ T cells in spleen, draining lymph nodes and especially in the tumors was promoted. Simultaneously, we exploited T cells depletion models to study the anti-tumor mechanisms for C25 peptide, and the results combined with MTT assay confirmed that C25 exerted anti-tumor effects via CD8⁺ T cells but not direct killing. In conclusion, cyclic peptide C25 provides a rationale for targeting the immune checkpoint, by blockade of LAG-3/HLA-DR interaction in order to enhance anti-tumor immunity, and C25 may provide an alternative for cancer immunotherapy besides antibody drugs.     

自体与异体CIK细胞抗肿瘤效应的对照研究

目的比较自体细胞因子诱导的杀伤细胞(CIK)与异体CIK细胞的抗肿瘤效应。方法外周血单个核细胞诱导CIK细胞,以自体细胞单独培养为对照。用MTT法测定杀伤活性,流式细胞术分析免疫表型,ELISA法测定干扰素-γ(IFN-γ)、白介素-12(IL-12)、肿瘤坏死因子-α(TNF-α)的水平。结果异体CIK细胞增殖能力明显高于自体CIK细胞(P<0.01),CD3+CD8+、CD3+CD56+细胞比率较相同条件下自体CIK细胞组显著增多(P<0.05),培养7 d,上清液中IL-12、IFN-γ、TNF-α水平均比自体CIK细胞培养的水平高(P<0.05),对白血病细胞与淋巴瘤细胞的杀伤率显著高于自体CIK细胞(P<0.01)。结论异体CIK细胞比自体CIK细胞有更强的抗肿瘤效应。     

How Well Can a T-Cell Epitope Replace Its Parent Carrier Protein? A Dose-Response Study

Purpose. This work examines the effectiveness of synthetic peptide immunogens derived from immunodominant T-cell epitopes as replacements for their intact parent protein in vaccines. Methods. Fluorescein was conjugated to hen egg lysozyme (FL-HEL, positive control) and three synthetic peptide immunogens: (a) murine B10.A (H-2^a) immunodominant T-cell epitope of HEL [FL-(T-cell epitope)]; (b) multiple antigenic peptide (MAP) multimer of this epitope {[FL-(T epitope)]_n-MAP, n = 2-4}; and (c) negative control MAP with T-cell epitope residues replaced with glycine [(FL-Gly₁₈)₄-MAP]. The dose response of each immunogen was examined over a 300-fold range in B10.A mice. The immune response was monitored using antifluorescein ELISA assays. Results. FL-(T epitope)'s immune response correlated positively with dose, with maximum response comparable to that of [FL-(T epitope)]_n-MAP, or FL-HEL. This trend was consistent across 1°, 2°, and 3° responses, although interanimal variability was higher in the latter two because of an all-or-none response in mice immunized with this peptide. [FL-(T epitope)]_n-MAP's immune response was consistently high and nearly dose independent, a trend observed across 1°, 2°, and 3° responses. FL-HEL's immune response correlated negatively to dose in the 1° response but was nearly dose independent in the 2° and 3° responses. The magnitude of these latter responses was comparable to that observed for [FL-(T epitope)]_n-MAP. (FL-Gly₁₈)₄-MAP did not elicit an immune response except at the highest dose. This trend was consistent across 1°, 2°, and 3° responses. Conclusions. The monomeric epitope was 300-fold less potent than its parent carrier protein, but increasing immunogen valency using MAP technology compensated totally for reduced potency. (FL-Gly₁₈)₄-MAP's lack of response at all but the highest dose strongly suggests that a specific immunodominant T-cell epitope sequence for HEL is necessary for successful peptide mimicry of HEL. This work also demonstrates the importance of quality assessment of commercial MAP core resins.     

Procyanidin,a kind of biological flavonoid,induces protective anti-tumor immunity and protects mice from lethal B16F10 challenge

Recently, increasing evidences show that procyanidin (PC) modulate immune responses in human. To evaluate adjuvant effects of PC on vaccine immune modulation and anti-tumor activity, we formulated PC with B16F10 tumor antigen as tumor vaccine to immune C57BL/6 mice and used intramuscular injection before challenge with tumor B16F10 cells. Our results revealed that PC enhanced T cell-mediated immune responses both in vitro and in vivo. Moreover, the B16F10 tumor vaccine induced some degree of anti-tumor effects as evaluated by the inhibition of tumor growth and the prolongation of survival. The tumor-bearing mice showed a high level of specific cytotoxic activity and had activated CD8 T cells that secreted perforin, IFN-γ and TNF-α in response to the stimulation with antigen in vitro. Taken together, current study presents evidence that PC may be used as a promising vaccine adjuvant.     

Transduction of the gene coding for a human G-protein coupled receptor FPRL1 in mouse tumor cells increases host anti-tumor immunity

Low antigenicity or development of tolerance is believed to be a major contributor to the escape of malignant tumors from immune surveillance of the host. However, anti-tumor responses can be elicited by concomitant immunization of poorly antigenic tumor cells with homologous xenogeneic proteins as 'altered self' proteins. In our study, anti-tumor, but not anti-xenogeneic antigen, immune responses were generated after transduction of the gene coding for a G-protein coupled human formyl peptide receptor like-1 (FPRL1) into a mouse C26 colon cancer cell line. C26 cells transfected with FPRL1 gene exhibited markedly reduced tumorigenicity in syngeneic mice, in association with the appearance of high levels of antibody activity reacting with both FPRL1 containing and wild type C26 cells. The anti-tumor responses required the participation of CD4+ T lymphocytes, since no tumor rejection was observed in nude mice or in syngeneic mice depleted of CD4+ T cells. Furthermore, mice primed with FPRL1 transfected C26 cells were resistant to subsequent challenge by wild type C26 cells. These results indicate that the presence of human FPRL1 is capable of triggering specific anti-tumor host immune responses against poorly antigenic mouse tumor cells.     

CpG oligodeoxynucleotide-adjuvanted fusion peptide derived from HBcAg epitope and HIV-Tat may elicit favorable immune response in PBMCs from patients with chronic HBV infection in the immunotolerant phase

The absence or insufficiency of specific immune response results in chronic hepatitis B virus (HBV) infection and immunotolerance. Therapeutic fusion peptide containing hepatitis B core antigen (HBcAg)(18-27) CTL epitope and human immunodeficiency virus (HIV)-Tat(49-57) peptide was synthesized and the activity when adjuvanted with CpG oligodeoxynucleotide (CpG ODN) was evaluated in PBMCs from patients with chronic HBV infection in the immunotolerant phase in this study. Results showed that the fusion peptide when adjuvanted with CpG ODN could induce significantly higher levels of IFN-γ and IL-4 in the PBMCs compared with fusion peptide or CpG ODN alone. The magnitude of augmentation to IFN-γ by the fusion peptide plus CpG ODN was much higher than that to IL-4. Cytotoxicity assay showed that the percentage of target cell lysis by effector cells stimulated by fusion peptide plus CpG ODN was higher than that in fusion peptide or CpG ODN alone at most of the E/T ratios tested. The magnitude augmented to IFN-γ by fusion peptide plus CpG ODN was also much higher than that to the percentage of target cell lysis. It is concluded that HBcAg(18-27) and HIV-Tat(49-57) fusion peptide when adjuvanted with CpG ODN may have much higher potency to induce IFN-γ than to induce IL-4 and cytotoxicity, suggesting the favorable immune response towards noncytolytic inactivation of the virus mediated by IFN-γ and the potential to break the tolerant state in chronic HBV infection.     

Evaluation of CD4+/CD8+ T-cell expression and IFN-γ, perforin secretion for B-T constructs of F1 and V antigens of Yersinia pestis

Yersinia pestis is a facultative bacterium that can survive and proliferate inside host macrophages and cause bubonic, pneumonic and systemic infection. Understanding the immune response generated by epitopes recognized by CD4+ and CD8+ T cells is important for the development of safe and effective vaccines designed to promote protective cellular immunity. Apart from humoral response, CD4+ T cells have shown to have a major role in combating the pneumonic form of the disease. In the present study, the secretion of IFN-γ and IL-4 by splenocytes, stimulated by different constructs of B and T cell epitopes of F1 and V antigens, was measured by ELISpot assay. We also measured perforin and IFN-γ expression as a function of cell mediated immunity by flow cytometry. Three B-T constructs of F1 and seven B-T constructs of V antigens produced a high number of IFN-γ secreting cells as compared to native antigen and a low number of IL-4 secreting cells. B-T conjugates of F1 and V antigens showed significantly high (p<0.001) percentage of CD4+ IFN-γ(+) cells as compared to CD8+ IFN-γ(+) cells. Thus, the study highlights the importance of Th1 cytokine and existence of high proportion of CD4+ T cells probably contributing protection in the host. This study proposes a new perspective for the development of vaccination strategies for Y. pestis that trigger T cell immune response.     

HIV gp41融合多肽对抗原特异性Treg活化的抑制作用

目的探讨HIV gp41融合多肽(fusion peptide,FP)与机体免疫细胞的相互作用,观察FP能否影响抗原特异性的调节性T细胞活化。方法用免疫磁珠分离DO11.10小鼠脾脏CD4+CD25+调节性T细胞(Treg)、CD4+CD25-效应性T细胞(Teff)共培养,3d后采用CCK-8法分析FP对OVA323-339抗原激活的Treg抑制Teff细胞增殖的影响。另外,ELISA法检测FP对Treg细胞IL-10分泌的影响,荧光共聚焦分析FP多肽在Treg细胞表面与TCR的共分布。结果25 mg·L-1的FP能降低Treg的抑制活性和IL-10分泌,在活化的Treg细胞表面有FP和TCR荧光的重叠。结论 FP降低抗原特异性Treg细胞的抑制功能,可能与其抑制IL-10合成有关;它与TCR在细胞膜的相互作用也可能影响APC向Treg细胞递呈活化信号,干扰Treg的活化。