Analysis of B cell and T cell proliferative responses induced by monomorphic and pleomorphic Trypanosoma brucei parasites in mice

Cells collected from C57B1/6 mice infected with monomorphic and pleomorphic clones of Trypanosoma brucei parasites (ILTat 1.4 and GUTat 3.1) were analysed for the incorporation of 125I-Iododeoxyuridine into DNA of total splenic lymphocytes and of B and T lymphocytes isolated on a fluorescence activated cell sorter. The monomorphic T. brucei ILTat 1.4 parasites triggered delayed and low splenic DNA synthetic responses in comparison to those arising in mice infected with the pleomorphic T. brucei GUTat 3.1 organisms. Mice infected with both parasite clones mounted splenic DNA synthetic responses similar to those arising in animals infected with the pleomorphic organisms alone and similar responses were induced by lethally irradiated T. bruceiGUTat 3.1 and T. brucei ILTat 1.4 parasites. In mice infected with the pleomorphic parasites, DNA synthesis was first detected in the T cell population and B cell DNA synthetic responses were detected between 1 and 2 days later. In contrast only T cell DNA synthetic responses were detected after infection with the monomorphic T. brucei ILTat 1.4 parasites. It is suggested that the previously reported failure of monomorphic T. brucei parasites to trigger antibody production in infected mice is a result of their inability to stimulate B lymphocytes.     

Suppressor macrophages in Trypanosoma brucei infection: nitric oxide is related to both suppressive activity and lifespan in vivo

African trypanosome infections cause immunosuppression in both experimental rodent and natural hosts. One characteristic of this is an eliciting of suppressor macrophages which results in an unresponsiveness in lymphocytes. Macrophages from Trypanosoma brucei-infected mice have previously been shown to produce high levels of nitric oxide (NO). Using model systems based on in vivo macrophage transfer and drug cure, we have sought to determine the relationship between NO and suppressed lymphocyte responses. Peritoneal macrophages from T. brucei-infected mice inhibited the Concanavalin A (Con-A) response of spleen cells from syngeneic recipients 3–4 days after transfer in vivo due to the activity of suppressor macrophages. When macrophage NO synthesis was inhibited either in vitro or in vivo the suppressive effects were partially abrogated. These data provide evidence of a role for NO in mediating immunosuppression during murine T. brucei infection. Suppression in spleens of mice receiving suppressor macrophages was transient, with total recovery of spleen cell mitogen responses six days after transfer. Suppression and recovery was found to coincide with the presence or absence (respectively) of donor macrophages in recipient spleens. When T. brucei-infected mice were treated with a curative dose of a trypanocide there followed a recovery of lymphocyte responsiveness after a period of 4–5 days, and this directly correlated with a reduction of macrophage NO synthesis to control levels both in vivo and in vitro. The apparent loss of suppressor macrophage activity after 4–6 days in both drug cured animals and recipients of macrophage transfer was shown to be due to NO-mediated apoptosis of these cells.     

Synthesis and secretion of immunoglobulin by spleen cells from resistant and susceptible mice infected with Trypanosoma brucei brucei GUTat 3.1

By 6 days after infection of susceptible C3H/He and resistant C57BL/6 mice with Trypanosoma brucei brucei GUTat 3.1, splenic plasma cell responses of both strains of mice were similar in terms of plasma cell number, intracellular Ig, Ig secretion, Ig class and Ig specificity for surface-accessible variant surface glycoprotein (VSG) epitopes on the infecting organisms, despite higher parasitaemia in the C3H/He mice. By 7 days after infection, however, although splenic plasma cells from both strains of mice had greatly amplified their Ig responses, those from C57BL/6 mice (which cleared parasites from their bloodstream between 6 and 7 days after infection) contained and secreted 3-5 times more Ig specific for exposed VSG epitopes on the infecting organisms than those from C3H/He mice which did not clear parasites from their bloodstream. In vitro, trypanosomes can absorb significant amounts of VSG-specific antibody produced by splenic plasma cells. However, differences in the detection of VSG-specific antibodies present in, and secreted by, splenic plasma cells of 7-day infected C3H/He and C57BL/6 mice were shown not to result from the presence of parasites in the cultures of C3H/He spleen cells. It is argued that between 6 and 7 days after infection, the C3H/He mice selectively lose the capacity to support development of plasma cells specific for exposed VSG epitopes on the infecting organisms and that this is a consequence rather than a cause of differences in the peak levels of first wave parasitaemia.     

Immunization with recombinant beta-tubulin from Trypanosoma evansi induced protection against T. evansi, T. equiperdum and T. b. brucei infection in mice

The beta-tubulin gene of Trypanosoma evansi (STIB 806) was cloned and expressed in Escherichia coli. The predicted amino acid sequence of T. evansi beta-tubulin shows 100%, 99.8%, 99.1%, and 98.6% homology with T. equiperdum, T. b. brucei, T. cruzi and T. danilewskyi, respectively, but is diverse from that of T. cyclops, showing only 51.6% of homology. Recombinant beta-tubulin was expressed as inclusion bodies in E. coli. It was purified and renatured for immunological studies. Mice immunized with the renatured recombinant beta-tubulin were protected from lethal challenge with T. evansi STIB 806, T. equiperdum STIB 818 and T. b. brucei STIB 940, showing 83.3%, 70% and 76.7% protection, respectively. Serum collected from the rabbit immunized with recombinant beta-tubulin inhibited the growth of T. evansi, T. equiperdum and T. b. brucei in vitro. Serum from mice and rabbits immunized with recombinant beta-tubulin recognized only T. evansi beta-tubulin and not mouse beta-tubulin. The results of this study demonstrated that the recombinant T. evansi beta-tubulin is a potential candidate for the development of a vaccine to prevent animal trypanosomiasis caused by these three trypanosome species.     

食管癌TDLN细胞对食管癌裸鼠移植瘤的体内抑瘤作用

目的探讨肿瘤引流区淋巴结细胞对食管癌裸鼠移植瘤的体内杀伤作用,为其临床应用提供依据。方法将30只食管癌移植瘤裸鼠模型随机分为对照组、IL-2组、LAK组、I-TDLN组及G-TDLN组。分别予生理盐水、IL-2、LAK细胞及体外培养的I-TDLN、G-TDLN细胞局部注射干预。分别于干预后1、2、3、4周测定各组肿瘤抑制率;干预后4周测定各组肿瘤细胞凋亡率;观察肿瘤组织病理学变化。结果 TDLN组各时点肿瘤抑制率均明显高于对照组、IL-2组及LAK组,G-TDLN组高于I-TDLN组（P均〈0.05）,各组肿瘤抑制率均逐渐升高,于第3周达高峰;对照组、IL-2组、LAK组、I-TDLN组、G-TDLN组细胞凋亡率依次升高,P均〈0.05。LAK组及TDLN组肿瘤组织均有T淋巴细胞和DC浸润,但TDLN组明显多于LAK组。结论体外培养的食管癌TDLN细胞在体内可抑制食管癌移植瘤生长,其机制为直接杀伤肿瘤细胞并诱导肿瘤细胞凋亡。本研究为食管癌TDLN细胞用于临床食管癌的细胞免疫治疗提供了理论依据。     

慢性乙型肝炎患者外周血NK细胞和T淋巴细胞计数变化及其临床意义

目的观察慢性乙型肝炎患者外周血NK细胞和T淋巴细胞数量的变化。方法在56例乙型肝炎肝衰竭、49例HBeAg阳性慢性乙型肝炎和41例乙型肝炎病毒携带者使用流式细胞仪检测外周血CD3+T细胞、CD3+CD4+T细胞、CD3+CD8+T细胞和NK(CD3-CD16+CD56+)细胞占淋巴细胞的比率(%)。结果肝衰竭患者CD3+T细胞和CD3-CD16+CD56+NK细胞计数比慢性乙型肝炎患者和乙型肝炎病毒携带者显著性降低(P0.05);慢性乙型肝炎患者CD3-CD16+CD56+NK细胞计数比乙型肝炎病毒携带者显著性升高(P0.05)。结论乙型肝炎肝衰竭患者外周血T细胞和NK细胞数量减少,而HBeAg阳性慢性乙型肝炎患者外周血T细胞数量增多。     

Systemic release of mucosal mast cell protease during infection with the intestinal protozoal parasite, Eimeria nieschulzi. Studies in normal and nude rats

The systemic secretion of rat mucosal mast cell protease (RMCPII), a major product of rat mucosal mast cells (MMC), was examined during primary infections with the protozoan parasite, Eimeria nieschulzi in CFH/B, athymic (rnu/rnu) and euthymic (rnu/+) rats. Release of RMCPII into the blood stream (2.9 micrograms/ml of serum) of normal rats occurred within 1 day after infection. This response developed 3-6 hours after inoculation with oocysts, was dose-dependent, and was found in both naive and immune rats. Maximal release of RMCPII (4.5 micrograms/ml of serum) in naive rats occurs 9 days after primary infection, whereas the numbers of MMC and concentrations of mucosal RMCPII were maximal 14 days after infection, by which time the systemic RMCPII response had begun to decline. The numbers of MMC and concentrations of mucosal RMCPII in uninfected nude rats were similar to those in the heterozygous (rnu/+) litter-mates. After infection, the numbers of MMC and concentrations of mucosal RMCPII increased in the heterozygotes but not in nude rats. Similarly, RMCPII was detected systemically only in the heterozygotes.     

Failure of nude (athymic) rats to become resistant to reinfection with the intestinal coccidian parasite Eimeria nieschulzi or the nematode Nippostrongylus brasiliensis

The course of each of three successive infections with Eimeria nieschulzi in nude (athymic) rats was the same as the primary infection in nu/+ animals, with the production of more oocysts. This indicates that resistance to reinfection with this parasite is mediated by T lymphocytes but that these cells do not control the duration of the life cycle, since oocyst production was not prolonged in the nu/nu rats. After the three infections with E. nieschulzi, the rats were exposed twice to the intestinal nematode Nippostrongylus brasiliensis, and the nu/nu were completely susceptible even to the second infection. Egg production by both infections in the nu/nu animals was similar and continued at a high plateau level for 28 days before falling to a low level. It appears that the strain of N. brasiliensis used in this study is unable to sustain high egg production for more than 4 weeks in T cell deficient rats.     

急性和慢性乙型肝炎患者外周血NK细胞和T淋巴细胞亚群的动态变化

目的：观察急性和慢性乙型肝炎患者急性期和恢复期外周血NK细胞和T淋巴细胞亚群的变化。方法在40例急性乙型肝炎和40例慢性乙型肝炎患者,分别在急性期和恢复期检测CD3＋CD4＋T细胞、CD3＋CD8＋T细胞和NK（CD3-CD16＋CD56＋）细胞占淋巴细胞的比率（%）。结果在急性乙型肝炎急性期NK细胞计数为（15.7±7.5）%,而在恢复期则上升至（21.9±8.2）%,（P＜0.05）;急性乙型肝炎患者在急性期CD3＋CD4＋T细胞为（35.5±6.8）%,到恢复期则显著下降（33.6±7.0）%,（P＜0.05）;急性乙型肝炎在急性期CD3＋CD8＋T细胞为（35.6±7.6）%,而在恢复期则显著下降（30.0±7.5）%,（P＜0.05）,后者仍比慢性乙型肝炎患者在病情恢复期高（19.1±7.1）%,（P＜0.05）。结论在急性乙型肝炎病程中,NK细胞呈上升趋势,CD3＋CD8＋T细胞呈下降趋势,而在慢性乙型肝炎患者NK细胞及T淋巴细胞数量下降,致病情迁延不愈。     

Trypanosoma cruzi: deficient lymphocyte reactivity during experimental acute Chagas'' disease in the absence of suppressor T cells

Infection of mice with Trypanosoma cruzi has been shown to lead to an impaired ability of lymphocytes to proliferate in response to mitogenic stimulation which is manifested during the acute period of the disease. A possible involvement of suppressor T lymphocytes has been postulated by other authors and was investigated in this work as a part of our efforts to disclose the mechanisms underlying the immunologic deficiency. Spleen cells from acutely infected CBA/J mice readily exhibited unresponsiveness to stimulation with concanavalin A, phytohaemagglutinin or a bacterial lipopolysaccharide. However, these cells were unable to reduce the responses that normal syngeneic-mouse spleen cells mounted to these mitogens when cultured together in equal proportions. Furthermore, removal of the Lyt 2.1-bearing cells, known to include the suppressor T cell subpopulation, from infected mouse splenocyte suspensions, did not alter the deficient responsive status of the remaining cells. These results, together with the severe depletion of the T-cell compartment which occurs in the spleens of animals acutely infected with T. cruzi, do not support an important role of suppressor T lymphocytes in the noted deficiency in lymphoid cell reactivity to mitogens. Reduced numbers of responder cells, intrinsic lymphocyte alterations or suppression by cells other than T lymphocytes remain plausible explanations to be explored.     

T cell-mediated immune response enhances the severity of myocarditis in secondary cardiotropic virus infection in mice

In this report, we showed that a previous enterovirus exposure in ordinary mice with normal T cell function, but not in T cell-deficient mice, can influence development of myocardial inflammation with a second virus exposure. Inoculation of 4-week-old male BALB/c-nu/+ (euthymic and normal T cell function) mice with amyocarditic Coxsackie virus B1 (CB1), followed by inoculation 28 days later with myocarditic variant of Coxsackie virus B3 (CB3-m) resulted in more intense myocardial inflammation and injury than was seen in BALB/c-nu/+ inoculated with CB1, followed by inoculation with non-enterovirus, i.e., encephalomyocarditis virus (EMC) or influenza A virus and in age-matched BALB/c-nu/+ mice secondary inoculated with CB3-m alone. In contrast, this phenomenon of the enhancement of the severity of myocarditis by a secondary CB3-m inoculation was not seen in BALB/c-nu/nu (athymic and T cell- deficient) mice. Interestingly, inoculation of BALB/c-nu/+ mice with CB1, followed by inoculation 28 days later with another amyocarditic variant of Coxsackie virus B3 (CB3-o), resulted in more severe myocarditis than was seen in age-matched BALB/c-nu/+ mice secondary inoculated CB3-o alone. Myocardial-activated T cells and elevated serum interleukin-6 were involved in the exacerbation of the disease during the reinfection. T cell-mediated immune responses to a conserved antigenic epitope among the enteroviruses may be involved in the exacerbation of myocardial inflammatory disease during a second enterovirus infection. Received: 14 December 2000, Returned for revision: 19 January 2001, Revision received: 30 January 2001, Accepted: 31 January 2001     

白细胞介素17介导致糖尿病性T细胞诱导的NOD小鼠糖尿病的发生

目的 研究白细胞介素17(IL-17)在致糖尿病性BDC2.5 T细胞转移性糖尿病发病中的作用.方法 通过注射转基因IL-17 BDC2.5 T细胞(IL-17组,n=6)、IL-17 siRNA BDC2.5 T细胞(silL-17组,n=5),观察高表达和低/无表达IL-17转基因BDC2.5 T细胞对NOD.scid小鼠转移性糖尿病的影响,进行小鼠胰岛组织学鉴定、脾脏和胰腺淋巴结染色和血浆细胞因子测定.非转基因BDC2.5 T细胞注射为对照组(n=8).结果 在观察期内,IL-17组小鼠全部发生糖尿病,而silL-17组和对照组则无一例发病.胰腺病理HE染色显示IL-17组小鼠出现严重的胰岛炎,胰岛受到破坏,结构模糊不清;而silL-17组小鼠胰腺仅表现为轻、中度胰岛炎,可见胰岛内散在的细胞浸润,胰岛组织结构基本完整,细胞形态正常.小鼠脾脏和淋巴结染色显示,IL-17组小鼠脾脏和胰腺淋巴结中CD11c+/CD11b+的树突细胞增殖显著高于silL-17组和对照组(均P＜0.01),且胰腺淋巴结中该细胞增殖显著高于脾脏.IL-17组小鼠血浆IL-17、肿瘤坏死因子α、γ-干扰素和白细胞介素6水平均显著高于siIL-17组和对照组(均P＜0.01),后两组间差异无统计学意义(P＞0.05).结论 BDC2.5 T细胞的IL-17高表达可显著加速NOD.scid小鼠发生转移性糖尿病,且与宿主树突细胞增殖和在胰腺淋巴结局部的聚集以及多种细胞因子作用有密切关系.     

Immunoregulation in experimental murine Trypanosoma congolense infection: anti-IL-10 antibodies reverse trypanosome-mediated suppression of lymphocyte proliferation in vitro and moderately prolong the lifespan of genetically susceptible BALB/c mice

We infected highly susceptible BALB/c and relatively resistant C57BL/6 mice with cloned Trypanosoma congolense and followed the effects of these infections on the circulating parasite numbers, mouse mortality and cytokine expression. C57BL/6 mice controlled their parasitaemia and survived for up to 163 ± 12 days, while BALB/c mice could not control their parasitaemia and succumbed to the infection within 8.4 ± 0.5 days. Susceptible BALB/c mice had dramatically higher plasma levels of IL-10 than the resistant C57BL/6 mice from day 7 forward. This was preceded by an earlier and higher level induction of splenic IL-10 messenger RNA (mRNA) expression in the infected BALB/c mice. There was a strong negative correlation between the splenocyte proliferative responses to Concanavalin-A (Con-A) and their production of IL-10 in these infected BALB/c mice. Co-treatment of the Con-A-stimulated spleen cell cultures with monoclonal anti-IL-10 antibodies, but not isotype-matched control antibodies, could completely reverse this suppression of the splenocyte proliferative response. Finally, in three experiments, anti-IL-10 antibody treatment in vivo reduced the peak circulating parasitaemia of infected BALB/c mice by 43% and increased their median survival periods by 38% relative to isotype-matched control antibody-treated mice .     

经树突状细胞递呈的HBcAg特异性细胞毒T淋巴细胞的体外研究

目的　从人的外周血树突状细胞 (DC)的抗原递呈方面研究慢性乙型肝炎的发病机制 ,并诱导出针对HBcAg特异性的细胞毒T淋巴细胞 (CTL)。方法　取健康人DC和患者DC ,比较两组的抗原递呈功能是否存在差异。以HBcAg体外冲击致敏DC ,与自体T淋巴细胞共育 ,诱导出HBcAg特异性CTL ;以HepG2细胞为对照靶细胞 ,转染HBVDNA的HepG2 2 15细胞为靶细胞 ,分别测定CTL在效靶比为 2∶1、6∶1和 2 0∶1时对HepG2细胞的非特异性杀伤率及对HepG2 2 15细胞的特异性杀伤率 ,并比较患者组与正常组特异性杀伤率的差异。结果　患者DC的抗原递呈功能(10 99.2 6 7± 2 39.12 ,1374 .8± 36 4 .15 5 ,2 717.78± 15 89.72 )较健康人 (314 7.933± 72 6 .5 7,384 3.0 0 0±10 6 0 .85 ,5 4 86 .86 7± 1790 .6 4 )弱 ;健康组与患者组CTL对HepG2各效靶比的非特异性杀伤作用差异无显著性。健康组与患者组CTL对HepG2 2 15的特异性杀伤作用差异有显著性 ;患者组CTL的活性 (7.1± 4 .33,15 .6 8± 3.3,2 7.6 6± 4 .5 9)较健康组 (2 0 .76± 6 .0 8,33.97± 8.0 0 ,4 9.6 3± 9.4 8)弱。结论　用HBcAg体外负载患者DC ,能诱导出抗原特异性的CTL ,这些CTL能特异性地杀伤相应靶细胞。     

Traffic of T and B Lymphocytes in the Normal Spleen

The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: T^E lymphocytes are found especially in the periarteriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous ⁵¹Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30 % of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periarteriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.     

Regulation of the growth and differentiation of Trypanosoma (Trypanozoon) brucei brucei in resistant (C57B1/6) and susceptible (C3H/He) mice

While Trypanosoma brucei brucei GUTat 3 were equally infective for C3H/He and for C57Bl/6 mice at doses ranging from 5 to 5 x 10(3) organisms and had similar prepatent periods in both strains of mice, infected C57Bl/6 mice displayed lower parasitaemia, shorter times to parasite wave remission and survived for a longer time than infected C3H/He mice. Parasite growth and differentiation rates and host immune responses were similar for the first 5 days in both strains of mice after infection with 10(3) T.b.brucei GUTat 3 but, thereafter, parasite differentiation proceeded more rapidly and specific antibodies reached higher titres in C57Bl/6 than in C3H/He mice. In contrast, parasite growth and differentiation rates were similar in irradiated mice of both strains. Furthermore, following inoculation of intact mice with irradiated T.b.brucei GUTat 3, C3H/He mice actually mounted higher titred antibody responses than C57Bl/6 mice showing that they were not intrinsically defective in their capacity to respond to GUTat 3 antigens. Parasite differentiation occurred at the same rate in irradiated (650r) C57Bl/6 mice and in irradiated C57Bl/6 mice reconstituted with syngeneic spleen cells although T.b.brucei GUTat 3 specific antibody was detected in the latter mice prior to peak parasitaemia. Furthermore, it was shown directly in C57Bl/6 mice that there was no selective destruction of slender form T.b.brucei GUTat 3 parasites during the phase of accumulation of stumpy form parasites. These studies indicate that the more rapid differentiation of T.b.brucei GUTat 3 parasites in infected C57Bl/6 mice as compared to infected C3H/He mice was unlikely to be directly related to the more efficient antibody response in the infected C57Bl/6 mice. The observations suggest that there might be an association between host mechanisms which regulate differentiation of T.b.brucei parasites and those which regulate antibody responses.     

不同阶段 HBV 相关 ACLF 患者外周血 DC 及T 淋巴细胞免疫功能特点研究

目的：比较不同阶段的 HBV 相关慢加急性（亚急性）肝衰竭（HBV-ACLF）患者外周血树突状细胞（DC）、T淋巴细胞（TC）相关细胞免疫功能,阐述 DC-TC 轴在 HBV-ACLF 发病过程中可能的细胞免疫学机制。方法HBV-ACLF患者30例,分为早期组15例与中晚期组15例,另设健康对照组8例,以外周血来源的 PBMC 体外分离诱导培养 DC 与TC,应用流式细胞计数检测 DC 细胞表型 HLA-DR、CD80、CD86、CD83、CD1α的表达率,及 TC 表面分子 CD3＋、CD4＋ T、CD8＋ T 淋巴细胞百分比,并检测 DC 上清液中 IFN-α、IL-4的分泌水平,比较不同阶段 HBV-ACLF 患者免疫细胞及炎性因子表达的差异。结果与健康人比较,HBV-CLF 患者 DC 表型 HLA-DR、CD1α、CD83、CD80、CD86表达率显著下降（t 值分别为5．3356、13．269、10．8742、13．3685和23．021,均 P ＜0．01）,DC 分泌因子 IFN-α显著升高（t 值为16．4569,P ＜0．01）;TC 表面分子 CD3＋、CD4＋ T、CD4＋／CD8＋细胞比值显著下降（t 值分别为7．4441、12．5557、11．0771,均 P ＜0．01）, CD8＋ T 细胞百分比显著上升（t＝4．4359,P ＜0．01）;HBV-ACLF 患者中晚期组 DC 表型 CD83、CD86表达率显著低于早期组（P 值分别为：0．0000,0．0057）,DC 分泌因子 IFN-α表达在早期组显著增多（P ＝0．0000）,IL-4表达在中晚期组显著增多（P ＝0．0000）,TC 表面分子中晚期组 CD4＋ T 细胞百分比、CD4＋／ CD8＋细 胞 比 值 显 著 下 降 （P 值分别为：0．0268、0．0002）,CD8＋ T 细胞百分比显著上升（P ＝0．0001）。结论不同阶段 HBV-ACLF 患者的 DC、TC 功能状态均表现为细胞免疫功能低下,中晚期患者的细胞免疫功能更为低下;HBV-ACLF 全病程存在促／抑炎性细胞因子功能紊乱,早期患者存在炎症因子过度释放,中晚期患者存在抗炎症细胞因子表达增强。     

慢性乙型肝炎的Th细胞亚群及相关细胞因子网络失衡

辅助性T细胞(helper T cell,Th细胞)是根据功能分类的一个T细胞亚群,根据所分泌细胞因子的不同,Th细胞可分为Th0、Th1、Th2和Th3 4种亚群,其中研究最多的是Th1和Th2两个亚群.Th1/Th2细胞及其细胞因子网络的调节对维持机体正常的免疫功能至关重要.乙型肝炎病毒(HBV)感染机体后,多种因素影响Th细胞增殖并且调节其亚型比例,细胞因子网络受到破坏,在细胞因子介导下便可造成肝脏等组织和器官的损害,直接或间接地影响到乙型肝炎发病及其转归.     

B lymphocyte function in multiple myeloma: analysis of T cell- and monocyte-dependent antibody production

T-cell and B-cell functions were studied in 35 patients with untreated multiple myeloma (MM) and in 16 patients with MM treated with prednisolone, melphalan and vincristine. The numbers of CD4+ T cells were normal in untreated MM patients, but markedly decreased in treated patients, whereas CD8+ cell numbers were normal in untreated and treated patients. Mitogen-induced as well as antigen-induced lymphocyte proliferative responses were reduced, but not further affected by treatment. The antigen-induced proliferative responses by lymphocytes of treated, but not of untreated patients, correlated positively to the proportions of CD4+ cells among MNC. Taken together, the findings suggest selective loss of CD4+ subpopulations during cytotoxic treatment. Pokeweed mitogen (PWM)-induced Ig production was generally low, but significantly reduced Ig production was only seen in experiments employing MM B cells and monocytes co-cultured with irradiated T-enriched cells. Irradiated MM T cells displayed normal helper function when co-cultured with normal B cells stimulated with PWM. MM B cells and monocytes cultured with irradiated normal T cells produced little Ig; however, MM monocytes were not suppressive. In 2 of 3 patients with either IgG-kappa or IgA-kappa myeloma, the numbers of PWM-stimulated B cells that produced kappa chains were somewhat higher than those found among normal MNC. The impaired ability of antibody production by B cells from untreated MM patients seems to relate to intrinsic B cell defect(s) rather than to abnormal regulation by T cells or monocytes. However, disturbances in the functions of CD4+ cells may be observed in treated MM.     

Evaluation of IFN-gamma production by CD8 T lymphocytes in response to the K1 peptide from KMP-11 protein in patients infected with Trypanosoma cruzi

The cellular response mediated by MHC class I restricted CD8+ T cells has been shown to be crucial in the control of Chagas disease. The K1 peptide derived from T. cruzi KMP-11 protein has a high binding affinity to the HLA-A*0201 molecule. Nevertheless, it is not known whether this peptide is processed and displayed as an MHC class I epitope during natural infection by T. cruzi. The aim of this study was to evaluate, by ELISPOT assay, the ability of K1 peptide to activate CD8+ T lymphocytes to produce IFN-gamma. Therefore, CD8+ T lymphocytes from 22 HLA-A*0201+ individuals, 12 chronic chagasic patients and 10 uninfected controls, were analysed. The results revealed that two of the chagasic patients had IFN-gamma-secreting CD8+ T cells that were able to respond to K1 peptide with a relative frequency of 110 and 230 per million CD8+ T cells. In contrast, none of HLA-A*0201+ uninfected controls responded to K1 peptide. Responses to HLA-A*0201 restricted peptide from the influenza matrix protein were found in six chagasic patients and four uninfected controls with an average frequency of 175 and 111 cells per million CD8+ T cells, respectively. Moreover, a flow cytometric assay for degranulation showed that chagasic responders had K1-specific cytotoxic CD8+ T cells. It is shown here for the first time that the K1 peptide is efficiently processed, presented and recognized by CD8+ T lymphocytes during the natural course of Chagas disease.