梅毒患者细胞免疫功能的检测及其临床意义
摘要
梅毒(syphilis)是由苍白螺旋体(Treponema pallidum)引起的慢性系统性传染病，属于性传播疾病(sexually transmitted disease，STD)，是经典性病的一种。临床表现甚为复杂，在其长期慢性过程中，症状显发与重复的潜伏相互交替。早期梅毒(感染在2年以内)传染性较大，是梅毒的主要传染源，病程越长，传染性越小，晚期梅毒(感染在2年以上)虽传染性小，但组织破坏严重。梅毒可累及全身任何组织器官，甚至可以造成残废。由于梅毒螺旋体体外培养困难，对其各方面的研究均受到限制，故其发病机制尚不完全清楚。治疗上一般采用1981年WHO提出的梅毒治疗方案，青霉素为治疗梅毒的首选药物，根据病程、病情的不同，所用剂量、疗程有所不同。近年来，随着国内梅毒患者发病率的逐年增高，有关该病的研究亦日益
一
增多。但相关研究多集中于梅毒的血清学检测及梅毒螺旋体抗
原性方面，而对梅毒患者本身的免疫状态却少有关注。虽然至
今尚未见到有关梅毒螺旋体对青霉素耐药的报道，但临床观察
发现，对于同样的治疗方案，患者皮损消退及快速血浆反应素
环状卡片试验（rapt plasma regain card test，RPR）转阴结果是不
一样的，从而考虑到每个患者自身免疫功能的差异。近年来，
免疫学的进展虽然很快，而在梅毒免疫学方面却进展不多。因
此人体感染梅毒螺旋体后的免疫反应性质目前仍不十分清楚，”
但确与体液免疫和细胞兔疫密切相关，这己从临床表现或动物
实验方面得到证实。本研究从细胞免疫的角度探讨患者的免疫
功能状态，研究其与病期、疗效间的关系，以期为更有效的治
疗及预后判定提供帮助。
材料与方法
通过流式细胞仪，运用标有异硫氰酸荧光素muorescein
lsothlocyanate，FITC）或藻红素（phycolerythrin，PE）的聚类分
化抗原（cluster of differentiation，CD）单抗，检狈了 46例梅毒
患者治疗前、后及20例正常人外周血T淋巴细胞免疫表型，
同时应用双抗体夹心ELISA法对同样对象测定了血清IL上及
JL上 水平。将治疗后三个月血清RPR阴转的患者设定为A
组，未阴转的患者设定为B组。分析了梅毒患者与正常对照组
细胞免疫功能的不同；不同病期梅毒患者的细胞免疫功能的差
别；以及不同的细胞兔疫功能与不同治疗效果间的关系。对实
验数据应用蚊SS门 刀）软件系统进行统计学处理，计量资料
用Z朽表示，多组资料比较采用方差分析，多个均数间的两两
郑州大学2002硕士学位论文 梅毒患者圳胞免疫功能的检测及其临床悬义
比较用q检验，两样本均数比较用矿检验，方差不齐时用矿’检
验，治疗前后用配对t检验，以P＜0刀5作为差异有显著性。
结果
1．梅毒患者治疗前细胞免疫功能与正常对照组比较：
CD。”、CD。”。N’K（CD；。”，CD，。“）细胞百分比、CD。”／CDs“比值及
血清L上水平明显降低（P叱．of）；CD。”细胞百分比、血清
SI＊－ZR水平均明显升高（P＜0刀1）。
2．各期梅毒患者治疗前细胞免疫功能与正常对照组比较
一期梅毒思者治疗前细胞兔疫功能与正常对照组相比：
CD3“、CD4”细胞百分比、CD4”／CDS”L值明显降低（P＜0刀 1）；
CD／细胞百分比、血清IL上及血清SIL2 水平明显升高
（P1刀1＼NK细胞百分比，两组相比差异无显著性意义
（＞0．05）。
二期梅毒患者治疗前细胞兔疫功能与正常对照组相比：
CD厂、CD。”、NK细胞百分Lll、CD。、CDs”［if值＆血清几－2水
平降低，差异均有显著性意义p刃＊）；CDS“细胞百分比及血
清 SIL上 水平升高，差异均有显著性意义o1刀 1人
潜伏梅毒患者治疗前细胞免疫功能与正常对照组柏比：
CD。十、CD。“、NK细胞百分比、CD。”／CD。“比值降低，差异有显
著性意义o＜0．of人 CDs”细胞百分比、血清dL上 水平升高，
差异有显著性意义0刃刀1＼卜2水平略降低，差异无显著性
意义（P＞0刀5）。
3．各期梅毒组治疗前细胞免疫功能组间的两两比较
一期、二期及潜伏期之间的各项指标比较显示：CD／、CD。’
3
——
细胞百分比及CD／CDs1值，三组患者之间无明显差异
0＞0刀5＼＊山“细胞百分比：二期及潜伏期组明显高于一期梅
毒组o叼刀1＼ 细胞百分比：二期梅毒组低于一期及潜伏
期组o1们人1卜2水平：一期梅毒组显著高于二期及潜伏期
组0功．01），h期梅毒组显著低于一期及潜伏期组01．01）；
SIL上 水平：h期梅毒组明显高于一期及潜伏期组0＜0．of人
4．A组（治疗后三个月RPR阴转组）患者治疗前、后细
胞免疫功能的变化
A组患者治疗前细胞免疫功能与正常对照组相比：CD厂。
CD。”细胞百分 Lll、CD。YCD。”Lh值降低（P＜0．01），CDs”细胞 i
分比、血清 SIL上 升高①叼刀 1），NK细胞百分比及血清 IL上
水平差异无显著性意义o叩刀5人
A组治疗后的细胞免疫功能与正常?
Syphilis, caused by Treponema pallidum^P), is a chronically, systematically and sexually transmitted disease(STD) with complicated clinic exhibition. During the long and chronic course of disease, patient's apparent symptoms alternate with latency ones. The early stage syphilis (less than 2 years), due to its strong infectivity is the main source of infection. Nevertheless, the advanced stage syphilis (more than 2 years), though the tissue destroyed seriously, comparatively has a little of infectivity. The longer the course of the disease has, the weaker the infectivity is. Syphilis can destroy every tissue or organic on people's body and even lead to lameness. Up to now , the real mechanism of this disease has not be found. The general treatment to syphilis is
recommended by WHO in 1981 is to use penicillin as the first choice only vary in dosage and period of treatment according to different course of disease and state of illness.
In recent years, along with the increasing incidences of domestic syphilis, more and more attention is paid to such disease. The study to this disease is mostly concentrated on the serum detection and antigen of Treponema pallidum for syphilis patient, few attention is paid to the immunity function of syphilis patient. However, in our clinical practice, disappearance destroyed skill and RPR seronegative differed from one patient to another under the same treatment, which made us consider and study whether or not that result was caused by the individual immunity difference. In recent years , though immunology progress greatly, the study to syphilis immunology has little advance. The immunity principle has not been cleared after patients receiving Treponema pallidum, but the close relationship between syphilis and immunity is clear. It is not difficulty to see from clinical that the course of disease is related to humoral immunity and cellular immunity no matter that is proved by either clinical expression or animal test. This dissertation, from the point of view of cellular immunity, studied the syphilis patient's immunity function and the relationship between the course of disease and treatment results so that it can be of much help to the more effective treatment and prognosis judgement.
Materials and methods:
With flow cytometry, using CD monoclonal antibodies labled by either fluorescein isothiocyanate (FITC) or phycolerythrin(PE), special feature of peripheral blood lymphocyte immunophenotypes (PBLI) was detected through pre-treatment and post-treatment of 46 cases of syphilitic patients and 20 cases of normal persons. Meanwhile, the same patients' IL-2 and sIL-2R serum level was detected by the ELISA method. After three month treatment, patients were divided into two groups according to their RPR result: group A, the seronegative; and group B, the seropositive. This report analyzed the difference of cellular immunity function between syphilis patients and normal group, and the one difference cellular immunity function among different courses of disease, even more the relationship between the different cellular immunity function and the different treatment results. Experiment data were statistically processed by computer with SPSS(10.0) software system, measure data were presented by x + s, analysis of variance(ANOVA)were used for multigroup materials and g-test were used to examine the discrepancy of multiple comparisons in multimeans , two sample means with Mest or t'-test to examine the notable discrepancy, pair Mest were used to examine the discrepancy of before and after treatment. Probability values less than 0.05 were considered statistically significant.
Results:
1 . Compared the cellular immunity function of syphilis patient before treatment with normal control persons', CD3+ cells, CD4+ cells, the ratio of CD4+/CD8+, NK(CD,6+, CD56+ )cells and the level of IL-2 in syphilic patients were significantly decreased ( P<0.01); but CD8+ cells and the level of sIL-2R significantly increased (P<0.01).
2. The comparison cellular immunity function of syph
一
增多。但相关研究多集中于梅毒的血清学检测及梅毒螺旋体抗
原性方面，而对梅毒患者本身的免疫状态却少有关注。虽然至
今尚未见到有关梅毒螺旋体对青霉素耐药的报道，但临床观察
发现，对于同样的治疗方案，患者皮损消退及快速血浆反应素
环状卡片试验（rapt plasma regain card test，RPR）转阴结果是不
一样的，从而考虑到每个患者自身免疫功能的差异。近年来，
免疫学的进展虽然很快，而在梅毒免疫学方面却进展不多。因
此人体感染梅毒螺旋体后的免疫反应性质目前仍不十分清楚，”
但确与体液免疫和细胞兔疫密切相关，这己从临床表现或动物
实验方面得到证实。本研究从细胞免疫的角度探讨患者的免疫
功能状态，研究其与病期、疗效间的关系，以期为更有效的治
疗及预后判定提供帮助。
材料与方法
通过流式细胞仪，运用标有异硫氰酸荧光素muorescein
lsothlocyanate，FITC）或藻红素（phycolerythrin，PE）的聚类分
化抗原（cluster of differentiation，CD）单抗，检狈了 46例梅毒
患者治疗前、后及20例正常人外周血T淋巴细胞免疫表型，
同时应用双抗体夹心ELISA法对同样对象测定了血清IL上及
JL上 水平。将治疗后三个月血清RPR阴转的患者设定为A
组，未阴转的患者设定为B组。分析了梅毒患者与正常对照组
细胞免疫功能的不同；不同病期梅毒患者的细胞免疫功能的差
别；以及不同的细胞兔疫功能与不同治疗效果间的关系。对实
验数据应用蚊SS门 刀）软件系统进行统计学处理，计量资料
用Z朽表示，多组资料比较采用方差分析，多个均数间的两两
郑州大学2002硕士学位论文 梅毒患者圳胞免疫功能的检测及其临床悬义
比较用q检验，两样本均数比较用矿检验，方差不齐时用矿’检
验，治疗前后用配对t检验，以P＜0刀5作为差异有显著性。
结果
1．梅毒患者治疗前细胞免疫功能与正常对照组比较：
CD。”、CD。”。N’K（CD；。”，CD，。“）细胞百分比、CD。”／CDs“比值及
血清L上水平明显降低（P叱．of）；CD。”细胞百分比、血清
SI＊－ZR水平均明显升高（P＜0刀1）。
2．各期梅毒患者治疗前细胞免疫功能与正常对照组比较
一期梅毒思者治疗前细胞兔疫功能与正常对照组相比：
CD3“、CD4”细胞百分比、CD4”／CDS”L值明显降低（P＜0刀 1）；
CD／细胞百分比、血清IL上及血清SIL2 水平明显升高
（P1刀1＼NK细胞百分比，两组相比差异无显著性意义
（＞0．05）。
二期梅毒患者治疗前细胞兔疫功能与正常对照组相比：
CD厂、CD。”、NK细胞百分Lll、CD。、CDs”［if值＆血清几－2水
平降低，差异均有显著性意义p刃＊）；CDS“细胞百分比及血
清 SIL上 水平升高，差异均有显著性意义o1刀 1人
潜伏梅毒患者治疗前细胞免疫功能与正常对照组柏比：
CD。十、CD。“、NK细胞百分比、CD。”／CD。“比值降低，差异有显
著性意义o＜0．of人 CDs”细胞百分比、血清dL上 水平升高，
差异有显著性意义0刃刀1＼卜2水平略降低，差异无显著性
意义（P＞0刀5）。
3．各期梅毒组治疗前细胞免疫功能组间的两两比较
一期、二期及潜伏期之间的各项指标比较显示：CD／、CD。’
3
——
细胞百分比及CD／CDs1值，三组患者之间无明显差异
0＞0刀5＼＊山“细胞百分比：二期及潜伏期组明显高于一期梅
毒组o叼刀1＼ 细胞百分比：二期梅毒组低于一期及潜伏
期组o1们人1卜2水平：一期梅毒组显著高于二期及潜伏期
组0功．01），h期梅毒组显著低于一期及潜伏期组01．01）；
SIL上 水平：h期梅毒组明显高于一期及潜伏期组0＜0．of人
4．A组（治疗后三个月RPR阴转组）患者治疗前、后细
胞免疫功能的变化
A组患者治疗前细胞免疫功能与正常对照组相比：CD厂。
CD。”细胞百分 Lll、CD。YCD。”Lh值降低（P＜0．01），CDs”细胞 i
分比、血清 SIL上 升高①叼刀 1），NK细胞百分比及血清 IL上
水平差异无显著性意义o叩刀5人
A组治疗后的细胞免疫功能与正常?
Syphilis, caused by Treponema pallidum^P), is a chronically, systematically and sexually transmitted disease(STD) with complicated clinic exhibition. During the long and chronic course of disease, patient's apparent symptoms alternate with latency ones. The early stage syphilis (less than 2 years), due to its strong infectivity is the main source of infection. Nevertheless, the advanced stage syphilis (more than 2 years), though the tissue destroyed seriously, comparatively has a little of infectivity. The longer the course of the disease has, the weaker the infectivity is. Syphilis can destroy every tissue or organic on people's body and even lead to lameness. Up to now , the real mechanism of this disease has not be found. The general treatment to syphilis is
recommended by WHO in 1981 is to use penicillin as the first choice only vary in dosage and period of treatment according to different course of disease and state of illness.
In recent years, along with the increasing incidences of domestic syphilis, more and more attention is paid to such disease. The study to this disease is mostly concentrated on the serum detection and antigen of Treponema pallidum for syphilis patient, few attention is paid to the immunity function of syphilis patient. However, in our clinical practice, disappearance destroyed skill and RPR seronegative differed from one patient to another under the same treatment, which made us consider and study whether or not that result was caused by the individual immunity difference. In recent years , though immunology progress greatly, the study to syphilis immunology has little advance. The immunity principle has not been cleared after patients receiving Treponema pallidum, but the close relationship between syphilis and immunity is clear. It is not difficulty to see from clinical that the course of disease is related to humoral immunity and cellular immunity no matter that is proved by either clinical expression or animal test. This dissertation, from the point of view of cellular immunity, studied the syphilis patient's immunity function and the relationship between the course of disease and treatment results so that it can be of much help to the more effective treatment and prognosis judgement.
Materials and methods:
With flow cytometry, using CD monoclonal antibodies labled by either fluorescein isothiocyanate (FITC) or phycolerythrin(PE), special feature of peripheral blood lymphocyte immunophenotypes (PBLI) was detected through pre-treatment and post-treatment of 46 cases of syphilitic patients and 20 cases of normal persons. Meanwhile, the same patients' IL-2 and sIL-2R serum level was detected by the ELISA method. After three month treatment, patients were divided into two groups according to their RPR result: group A, the seronegative; and group B, the seropositive. This report analyzed the difference of cellular immunity function between syphilis patients and normal group, and the one difference cellular immunity function among different courses of disease, even more the relationship between the different cellular immunity function and the different treatment results. Experiment data were statistically processed by computer with SPSS(10.0) software system, measure data were presented by x + s, analysis of variance(ANOVA)were used for multigroup materials and g-test were used to examine the discrepancy of multiple comparisons in multimeans , two sample means with Mest or t'-test to examine the notable discrepancy, pair Mest were used to examine the discrepancy of before and after treatment. Probability values less than 0.05 were considered statistically significant.
Results:
1 . Compared the cellular immunity function of syphilis patient before treatment with normal control persons', CD3+ cells, CD4+ cells, the ratio of CD4+/CD8+, NK(CD,6+, CD56+ )cells and the level of IL-2 in syphilic patients were significantly decreased ( P<0.01); but CD8+ cells and the level of sIL-2R significantly increased (P<0.01).
2. The comparison cellular immunity function of syph
引文
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25． Pavia CS, Niederbuhl CJ. Adoptive transfer of anti-syphilis immunity with lymphocytes from Treponema pallidum-infected guinea pigs.J Immunol, 1985, 135(4) : 2829-2834 .
26． Hindersson P, Knudsen J D,Axelsen N H. Cloning and expression of T pallidum common antigen(Tp-4) in escherichia coli K12． J Gen Microbiol,1987;133:58
27． Podwinska J.The role of humoral and cell-mediated immunity in protection against Treponema pallidum infection. Arch Immunol Ther Exp(Warsz), 1993,41(5-6) : 281-284． Review.
28． Wicher K,Miller JN, Urquhart AW. Treponema pallidum immobilizing antibodies in guinea pig experimental syphilis.Infect Immun.1989,57(9) :2900-2902．
29．陆德源．现代免疫学．第1版，上海：上海科学技术出版社，1995，237-238
30. Tseraidi NF. Immunosuppression in patients with syphilis and problems of human immunodeficiency virus infection. Acta Derm Venereol, 1994,74(4):317-319.
31. Engelkens HJ, van der Sluis JJ, Stolz E. Syphilis in the AIDS era. Int J Dermatol. 1991,30(4):254-256.
32．白常禾译 血型与梅毒地方病译丛 1989；(6)：50-51
33. Baker-Zander SA, Fohn MJ, Lukehart SA. Development of cellular immunity to individual soluble antigens of Treponema pallidium during experimental syphilis. J Immunol, 1988, 141:4363-4369
34. Pope V, Sandffre ZL,Larson SA, et al. Flow cytometric of peripheral blood lymphocyte immunophenotypes in persons infected with Treponema pallidum. ClinDiagn Lab immunol, 1994,1: 121-124.s
35．林飞卿，等．医学基础免疫学．上海：上海医科大学出版社，1990，134-138
36. Trinchieri G, Matsumoto KM, Clark S, et al. Response of resting human perpherial blood natural killer cells to interleukin-2. J Exp Med, 1984,160:1147-1169
37. Podwinska J, Lusiak M, Zaba R,et al. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. FEMS Immunol Med Microbiol 2000,28(1):1-14
38．曹双林，傅玲玲，符梅，等．二期梅毒患者血清白介素6、白介素8及肿瘤坏死因子α测定．中华皮肤科杂志，2001，34(6)：423-424．
39. Lusiak M, Podwinska J. Interleukin 10 and its role in the regulation of the cell-mediated immune response in syphilis. Arch Immunol Ther Exp (Warsz) 2001, 49(6):417-421.
40．邓安梅．Th细胞分化研究进展．国外医学免疫学分册，1998，21(3)：161-163．
41. De Weal-Malefyt R, Yssel H, de Vries JE.Direct effects of IL-1Don subsets of human CD_4 Tcell clones and resting T cells: specific inhibition of IL-2production and proliferation. J Immunol, 1993, 150:4754
42. Hsu DH, Moore KW, Spits H. Differential effects of IL-4 and IL-10 on IL-2 induced IFN-gamma synthesis and lymphokine-activated killer activity. Int Immunol, 1992,4:563
43. Fiorentino DF, Bond NW, Mosman TR, et al. Two types of mouse T helper cell. Ⅳ. The clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989,170(6):2081-2095.
44. Nelson DL, warner C. Expression of soluboe from of IL-2 receptor and neoplastic states. Ann Inter Med, 1986,105:560-564
45．富宁，朱迅．可溶性白细胞介素2受体及其生物学意义．国外医学免疫学分册 1989，12：225-228
46. Podwinska. The ability of peripheral blood mononuclear cells (PBMC) of syphilitic patients to produce IL-2. FEMS-Immunol-Med-Microbiol. 1995,Sep; 12(1):17-27
47. Fitzgerald TJ, Tamai MA, Splenic T-lymphocyte functions during early syphilitic infection are complex. Infect Immunl 1991,59(11):4180-4186.
48. Van Voorhis WC, Barrett LK, Koelle DM, et al. Primary and Secondary
syphilis lesions contain mRNA for Thl cytokines. J-Infect-Dis.1996 Feb;173(2) :491
49． Fitzgerald TJ, Tomai MA, Trachte GJ, et al. Prostaglandins in experimental syphilis: trponemes stimulate adherent spleen cells to secrete prosftagljandin E2 and indomethacin upregulates immue functions. Infect-Immun.1991 Jani; 59(1) : 143
50． Wicher V, Scarozza AM, Ramsingh AI, et al. Cytokine gene expression in skin of susceptible guinea pig knfected with Treponema pallidum. Immunology 1998,95(2) : 242-247
51． 武明昌，朱慧兰，林蔼，等。梅毒患者血清sIL-2R水平的变化及其临床意义。临床皮肤科杂志 1999,28 (3) :167
2. Johnson PC, Farnie MA. Testing for syphilis. Dermatol Clin, 1994,12:9-177.
3. Laren SA. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev, 1995,8:1
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5. Young H, Petras V, Barrett JT, et al. Immunological Diagnosis of Sexually Transmitted Diseases, 1988, 241-218 Macel Dekker
6． 刘辅仁．实用皮肤科学 第2版 北京：人民卫生出版社，1996，621-640
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8. Zenkea PN, Rolfs RT. Treatment of syphilis, Reviews of Infectious Diseases, 1990,12(Suppl 6): 590
9. Borisenko KK, Loseva OK, Bondarenko TF, et al. Long-term outcomes of sumamed therapy of early syphilis(Russ), Vestin Dermatol, 1997,(2):42
10. Akovbyan VA, Kubanov AA, Dmitriev GA. Ceftriaxon (rocefin) in therapy of syphilis (Russ). Vestin Dermatol, 1997,(3):27.
11. Kanda T, Shinohara H, Suzuki T, etal. Depressed CD_4/CD_8 ratio in TPHA-negative patients with syphilis. Microbiol Immunol,1992,36:317.
12. Jaffe HW, Musher DM. Management of thereactive syphilis serology. In: Holmes KK eds. Sexually transmitted disease. 2 nd ed. New York: McGraw-Hill, 1990,935-939
13．李秋香译 梅毒螺旋体的致病性和免疫生物学．国外医学微生物学分册1988，(4)：179-183
14. Ware JL, Fold JD, Baseman JB. Modulation of normal lymphocyte stimulation serum from Treponema pallidum-infected rabbits. Cell immunol, 1980,53:29-38.
15. Marra C, Baker-Zander SA, Hook EW 3ed. An experimental model of early central nervous system syphilis. J Infect Dis. 1991,163(4):825-829.
16．金伯泉主编 细胞和分子免疫学．第1版，北京：世界图书出版公司，1998，142-144．
17．余传霖译 梅毒发病机理和疫苗设计国外医学微生物学分册 1994，17(4)：175-177
18．白常乐 梅毒在增加吗 地方病译丛 1994，15(3)：55-57
19. Arroll TW, Centurion Lara A, Lukehart SA, et al. T cell response to Treponema pallidum subsp.pallidum antigens during the course of experimental syphilis infection. Infect Immun. 1999,67(9):4757-4763.
20. Podwinska J, Lusiak M, Zaba R, et al. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. FEMS Immunol Med Microbiol 2000,28(1):1-14.
21． Van-Voorhis WC, Barrett LK. Rice RJ, et al. Primary and secondary syphilis lesions contain mRNA for Thl cytokines .J Infect Dis, 1996,73(1) : 491-495．
22． Podwinska J, Zaba R, Chomik M, et al. The ability of peripheral blood monomuclear cells (PBMC) of syphilitic patients to produce IL-2, FEMS immunol Med Midcrobiol, 1995, 12(2) : 17-27．
23． Haidoushka I, Rueva C, Zlatev S. An immunological study of syphilis patients. Folia Med(Plovdiv).1991,33(l):29-32．
24． Tanaka S , Suzuki T. Anti-Treponema pallidum IgM, IgA, and IgG subclass antibody responses after treatment in patients with syphilis at various stages:1． Assessments by enzyme-linked immunosorbent assay. Genitourin Med, 1990, 66: 171-177
25． Pavia CS, Niederbuhl CJ. Adoptive transfer of anti-syphilis immunity with lymphocytes from Treponema pallidum-infected guinea pigs.J Immunol, 1985, 135(4) : 2829-2834 .
26． Hindersson P, Knudsen J D,Axelsen N H. Cloning and expression of T pallidum common antigen(Tp-4) in escherichia coli K12． J Gen Microbiol,1987;133:58
27． Podwinska J.The role of humoral and cell-mediated immunity in protection against Treponema pallidum infection. Arch Immunol Ther Exp(Warsz), 1993,41(5-6) : 281-284． Review.
28． Wicher K,Miller JN, Urquhart AW. Treponema pallidum immobilizing antibodies in guinea pig experimental syphilis.Infect Immun.1989,57(9) :2900-2902．
29．陆德源．现代免疫学．第1版，上海：上海科学技术出版社，1995，237-238
30. Tseraidi NF. Immunosuppression in patients with syphilis and problems of human immunodeficiency virus infection. Acta Derm Venereol, 1994,74(4):317-319.
31. Engelkens HJ, van der Sluis JJ, Stolz E. Syphilis in the AIDS era. Int J Dermatol. 1991,30(4):254-256.
32．白常禾译 血型与梅毒地方病译丛 1989；(6)：50-51
33. Baker-Zander SA, Fohn MJ, Lukehart SA. Development of cellular immunity to individual soluble antigens of Treponema pallidium during experimental syphilis. J Immunol, 1988, 141:4363-4369
34. Pope V, Sandffre ZL,Larson SA, et al. Flow cytometric of peripheral blood lymphocyte immunophenotypes in persons infected with Treponema pallidum. ClinDiagn Lab immunol, 1994,1: 121-124.s
35．林飞卿，等．医学基础免疫学．上海：上海医科大学出版社，1990，134-138
36. Trinchieri G, Matsumoto KM, Clark S, et al. Response of resting human perpherial blood natural killer cells to interleukin-2. J Exp Med, 1984,160:1147-1169
37. Podwinska J, Lusiak M, Zaba R,et al. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. FEMS Immunol Med Microbiol 2000,28(1):1-14
38．曹双林，傅玲玲，符梅，等．二期梅毒患者血清白介素6、白介素8及肿瘤坏死因子α测定．中华皮肤科杂志，2001，34(6)：423-424．
39. Lusiak M, Podwinska J. Interleukin 10 and its role in the regulation of the cell-mediated immune response in syphilis. Arch Immunol Ther Exp (Warsz) 2001, 49(6):417-421.
40．邓安梅．Th细胞分化研究进展．国外医学免疫学分册，1998，21(3)：161-163．
41. De Weal-Malefyt R, Yssel H, de Vries JE.Direct effects of IL-1Don subsets of human CD_4 Tcell clones and resting T cells: specific inhibition of IL-2production and proliferation. J Immunol, 1993, 150:4754
42. Hsu DH, Moore KW, Spits H. Differential effects of IL-4 and IL-10 on IL-2 induced IFN-gamma synthesis and lymphokine-activated killer activity. Int Immunol, 1992,4:563
43. Fiorentino DF, Bond NW, Mosman TR, et al. Two types of mouse T helper cell. Ⅳ. The clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989,170(6):2081-2095.
44. Nelson DL, warner C. Expression of soluboe from of IL-2 receptor and neoplastic states. Ann Inter Med, 1986,105:560-564
45．富宁，朱迅．可溶性白细胞介素2受体及其生物学意义．国外医学免疫学分册 1989，12：225-228
46. Podwinska. The ability of peripheral blood mononuclear cells (PBMC) of syphilitic patients to produce IL-2. FEMS-Immunol-Med-Microbiol. 1995,Sep; 12(1):17-27
47. Fitzgerald TJ, Tamai MA, Splenic T-lymphocyte functions during early syphilitic infection are complex. Infect Immunl 1991,59(11):4180-4186.
48. Van Voorhis WC, Barrett LK, Koelle DM, et al. Primary and Secondary
syphilis lesions contain mRNA for Thl cytokines. J-Infect-Dis.1996 Feb;173(2) :491
49． Fitzgerald TJ, Tomai MA, Trachte GJ, et al. Prostaglandins in experimental syphilis: trponemes stimulate adherent spleen cells to secrete prosftagljandin E2 and indomethacin upregulates immue functions. Infect-Immun.1991 Jani; 59(1) : 143
50． Wicher V, Scarozza AM, Ramsingh AI, et al. Cytokine gene expression in skin of susceptible guinea pig knfected with Treponema pallidum. Immunology 1998,95(2) : 242-247
51． 武明昌，朱慧兰，林蔼，等。梅毒患者血清sIL-2R水平的变化及其临床意义。临床皮肤科杂志 1999,28 (3) :167