血清IL-6、IL-8、IgM抗体及T细胞亚群水平对新生儿先天性梅毒的诊断价值

目的:探讨血清白介素-6(IL-6)、白介素-8(IL-8)、IgM抗体及T细胞亚群对先天性梅毒新生儿的诊断价值。方法:选择2015年5月至2017年5月在我院进行临床治疗的先天性梅毒新生儿81例为观察组,另选同期来我院进行健康体检81例新生儿为对照组。比较两组患者血清IL-6、IL-8、T细胞亚群中CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)细胞及IgM抗体的阳性率。结果:治疗后,观察组血清IL-6、IL-8水平均明显高于对照组(P0.05),T细胞亚群中CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)明显低于对照组,而CD~(8+)T细胞比例高于对照组(P0.05)。19S-IgM-TP ELISA法检测出IgM的阳性率92.59%,明显高于TRUST法(74.07%)及TP-ELSA法(70.37%)(P0.05)。ROC曲线中,血清IL-8特异度为88.34%明显高于血清IL-6特异度81.48%、IgM抗体特异度60.13%、T细胞亚群特异度65.34%;IgM抗体的曲线面积88.91 cm~2明显大于IL-6的曲线面积45.09 cm~2、IL-8的曲线面积76.19 cm~2、T细胞亚群的曲线面积77.35 cm~2;T细胞亚群准备性67.89%明显高于IL-6准确性60.39%、IL-8准确性51.09%、IgM抗体准确性50.12;IgM抗体的灵敏度60.13%高于IL-6灵敏度59.19%、IL-8灵敏度42.35%、T细胞亚群灵敏度59.37%。具有比较意义(P0.05)。结论:血清IL-6、IL-8水平、T细胞亚群中CD~(3+)、CD~(4+)、CD~(8+)、CD~(4+)/CD~(8+)及IgM抗体阳性率是诊断先天性梅毒新生儿的重要指标。     

Trichinella spiralis: infection reduces airway allergic inflammation in mice

In an effort to define the mechanism underlying the host immune downregulation inherent to Trichinella spiralis infection, we compared the levels of Th1, Th2, and regulatory cytokines and CD4⁺CD25⁺ forkhead box P3 (FoxP3)⁺ T (T_reg) cell recruitment, as well as cellular pathology in the airway between T. spiralis infected and uninfected asthma-induced mice. After the induction of allergic airway inflammation, we noted influxes of inflammatory cells into the peribronchial tree. However, in the T. spiralis infection groups, cellular infiltration was minimal around the bronchial tree, with only a smattering of inflammatory cells. In the OVA-challenged group after T. spiralis infection, the numbers of macrophages and eosinophils in the bronchial alveolar lavage fluid were reduced by 23% and 52%, respectively, as compared to those of the OVA-challenged group. Airway hyperresponsiveness of OVA-challenged mice after T. spiralis infection was significantly suppressed as compared to the OVA-only challenged mice. The T. spiralis-infected mice exhibited a significant reduction in IL-5 concentrations relative to that noted in the OVA-challenged group (p < 0.01). Nevertheless, the regulatory cytokines IL-10 and TGF-β levels were increased significantly as the result of T. spiralis infection, and we verified the recruitment of T_reg cells in lung draining lymph nodes via T. spiralis infection. Therefore, T_reg cells, which were recruited by T. spiralis infection, might ameliorate lung function and reduce allergic airway inflammation.     

Natural CD825 regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

Natural CD4⁺25⁺ and CD8⁺25⁺ regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8⁺25⁺ Tr cells from C57BL/6 mouse naive CD8⁺ T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO_Tr) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO_Tr had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC_OVA) plus Tr cells or EXO_Tr, and then assessed OVA-specific CD8⁺ T cell responses using PE-H-2K^b/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10_OVA melanoma cells. We demonstrated that DC_OVA-stimulated CD8⁺ T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC_OVA (p < 0.05) in immunized mice with co-injection of Tr cells and EXO_Tr, respectively. Our results indicate that natural CD8⁺25⁺ Tr cell-released EXOs, alike CD8⁺25⁺ Tr cells, can inhibit CD8⁺ T cell responses and antitumor immunity. Therefore, EXOs derived from natural CD4⁺25⁺ and CD8⁺25⁺ Tr cells may become an alternative for immunotherapy of autoimmune diseases.     

Protective immunity against Leishmania major induced by Leishmania tropica infection of BALB/c mice

Leishmania (L.) tropica is a causative agent of human cutaneous and viscerotropic leishmaniasis. Immune response to L. tropica in humans and experimental animals are not well understood. We previously established that L. tropica infection induces partial protective immunity against subsequent challenge infection with Leishmania major in BALB/c mice. Aim of the present study was to study immunologic mechanisms of protective immunity induced by L. tropica infection, as a live parasite vaccine, in BALB/c mouse model. Mice were infected by L. tropica, and after establishment of the infection, they were challenged by L. major. Our findings shows that L. tropica infection resulted in protection against L. major challenge in BALB/c mice and this protective immunity is associated with: (1) a DTH response, (2) higher IFN-γ and lower IL-10 response at one week post-challenge, (3) lower percentage of CD4⁺ lymphocyte at one month post-challenge, and (4) the source of IFN-γ and IL-10 were mainly CD4⁻ lymphocyte up to one month post-challenge suggesting that CD4⁻ lymphocytes may be responsible for protection induced by L. tropica infection in the studied intervals.     

Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells

Cimetidine (CIM), a histamine 2-receptor antagonist, is postulated to enhance immune responses owing to its inhibitory effects on suppressor T cells. In this report, we evaluated effects of cimetidine on the potency of antigen-specific immunity generated by DNA vaccine encoding hepatitis B surface antigen (HBsAg, pcD-S2). Our data demonstrate that CIM as adjuvant significantly increased HBsAg-specific cell-mediated and humoral immunities that were characterized by higher Ig2a/IgG1 ratio. In addition, CIM significantly promotes an elevated level of IL-4 and IFN-γ in antigen-specific CD4⁺ T cells and a robust antigen-specific cytotoxic response in the animals immunized with pcD-S2 plus CIM. Further, CIM induces pro-inflammatory cytokine expression such as the IL-12 and down-regulates anti-inflammatory cytokine expression such as IL-10 and TGF-β, which may lead to an impairment of CD4⁺CD25⁺ Treg cell-mediated suppression. Collectively these findings suggest that CIM enhances the immune responses of HBV DNA vaccine through the stimulation of pro-inflammatory and inhibition of anti-inflammatory cytokine expression patterns.     

Enhancement of Th1 immune response by CD8α dendritic cells loaded with heat shock proteins enriched tumor extract in tumor-bearing mice

The discovery of dendritic cells (DCs) as professional antigen presenting cells has opened up new possibilities for their use in the development of tumor vaccines. We investigated the effect of the CD8α⁺ DCs loaded with heat-treated tumor lysate (HTL) as a vaccine in tumor immunotherapy. The HTL loaded CD8α⁺ DCs, TL loaded CD8α⁺ DCs and unloaded CD8α⁺ DCs were subcutaneously injected in the fibrosarcoma-bearing mice. The splenocyte proliferation and the shifting of Th1/Th2 response were measured. The results indicated a significant increase in the lymphocytes proliferation and the IFN-γ production in the test group of mouse splenocytes. According to the results, HTL loaded CD8α⁺ DCs vaccine significantly decreased tumor growth and longer survival than the other immunized animals. These findings show that anti-tumor immune response against the fibrosarcoma can be induced by HTL loaded CD8α⁺ DCs and may provide a useful therapeutic model for development of approaches to tumor treatments.     

Elimination of CD4+ T cells in mice bearing an advanced sarcoma augments the antitumor action of interleukin-2

Experiments were undertaken to determine whether the depletion of CD4⁺ T cells from mice bearing an advanced immunogenic SA-1 sarcoma would result in an enhanced ability of interleukin-2 (IL-2) to cause tumor regression. The results show that whereas IL-2 therapy given as a 5-day course starting on day 10 of tumor growth caused complete regression of the tumor, it failed to cause regression if started on day 15 of tumor growth. However, in mice depleted of CD4⁺ T cells by treatment with anti-CD4 monoclonal antibody (mAb), IL-2 therapy started on day 15 resulted in appreciable tumor regression in most animals, and the therapeutic effect was greatly increased if two consccutive courses of anti-CD4 mAb and IL-2 therapy were given. On the other hand, treatment with anti-CD4 mAb alone had no effect on tumor growth. It was shown that the therapeutic action of combination therapy with anti-CD4 mAb and IL-2 was mediated by CD8⁺ T cells, because the therapeutic effect was completely ablated in mice depleted of CD8⁺ T cells with anti-CD8 mAb. Taken together these results suggest that, at a late stage of growth of an immunogenic tumor, depletion of CD4⁺ T cells can enhance the antitumor effect of IL-2 therapy by releasing CD8⁺-T-cell-mediated immunity from T-cell-mediated suppression.     

In the FVB/N HER-2/<Emphasis Type="Italic">neu</Emphasis> transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by <Emphasis Type="Italic">Listeria monocytogenes</Emphasis>-based vaccines

Listeria monocytogenes-based vaccines for HER-2/neu are capable of breaking tolerance in FVB/N rat HER-2/neu transgenic mice. The growth of implanted NT-2 tumors, derived from a spontaneously occurring tumor in the FVB/N HER-2/neu transgenic mouse, was significantly slower in these mice following vaccination with a series of L. monocytogenes-based vaccines for HER-2/neu. Mechanisms of T cell tolerance that exist in these transgenic mice include the absence of functional high avidity anti-HER-2/neu CD8⁺ T cells and the presence of CD4⁺CD25⁺ regulatory T cells. The in vivo depletion of these regulatory T cells resulted in the slowing in growth of tumors even without the treatment of mice with an anti-HER-2/neu vaccine. The average avidities of responsive CD8⁺ T cells to six of the nine epitopes in HER-2/neu we examined, four of which were identified in this study, are shown here to be of a lower average avidity in the transgenic mice versus wild type FVB/N mice. In contrast, the average avidity of CD8⁺ T cells to three epitopes that showed the lowest avidity in the wild-type mice did not differ between wild type and transgenic mice. This study demonstrates the ability of L. monocytogenes-based vaccines to impact upon tolerance to HER-2/neu in FVB/N HER-2/neu transgenic mice and further defines some of the aspects of tolerance in these mice.     

Concanamycin A, a vacuolar type H+-ATPase inhibitor, induces cell death in activated CD8+ CTL

Concanamycin A (CMA) and concanamycin B (CMB) are specific inhibitors of vacuolar type H⁺-ATPase (V-ATPase). In our previous studies, intraperitoneal injection of CMB was shown to suppress the increase in CD8⁺ CTL population, but not to affect CD4⁺ and B220⁺ populations, in mice immunized with allogeneic tumors. To clarify the molecular basis of the selective decrease in the CD8⁺ CTL population by CMB, we have performed a series of in vitro experiments with use of CMA. Cell viability of the CD8⁺ population prepared from the immunized mice was preferentially decreased by CMA treatment. Moreover, in the CD8⁺ CTL clone, CMA induced a marked DNA fragmentation and nuclear condensation characteristic of apoptosis. Anti-CD3 or phorbol ester accelerated the CMA-induced reduction in cell viability of the CD8⁺ CTL clone, but not CD4⁺ T cell clones. However, this rapid cell death was not accompanied by DNA fragmentation and nuclear condensation. Perforin and granzyme B were unlikely to be involved in such cell death. Thus, our data suggest that V-ATPase activity is essential for survival of CD8⁺ CTL especially when activated. This revised version was published online in June 2006 with corrections to the Cover Date.     

A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+ T regulatory cells that promotes skin allograft survival in mice

Semimature dendritic cells (smDCs) can induce autoimmune tolerance by activation of host antigen-specific CD4⁺CD25⁺ regulatory T (Treg) cells. We hypothesized that donor smDCs injected into recipients would induce effector T-cell hyporesponsiveness by activating CD4⁺CD25⁺Treg cells, and promote skin allograft survival. Myeloid smDCs were derived from C57BL/6J mice (donors) in vitro. BALB/c mice (recipients) were injected with smDCs to generate antigen-specific CD4⁺CD25⁺Treg cells in vivo. Allograft survival was prolonged when BALB/c recipients received either C57BL/6J smDCs prior to grafting or C57BL/6J smDC-derived CD4⁺CD25⁺Treg cells post-grafting, and skin flaps from these grafts showed the highest IL-10 production regardless of rapamycin treatments. Our findings confirm that smDCs constitute an independent subgroup of DCs that play a key role for inducing CD4⁺CD25⁺Treg cells to express high IL-10 levels, which induce hyporesponsiveness of effector T cells. Pre-treating recipients with donor smDCs may have potential for transplant tolerance induction.     

CpG-C ODN M362 as an immunoadjuvant for HBV therapeutic vaccine reverses the systemic tolerance against HBV

Chronic Hepatitis B virus (CHB) infection is a global public health problem. Oligodeoxynucleotides (ODNs) containing class C unmethylated cytosine-guanine dinucleotide (CpG-C) motifs may provide potential adjuvants for the immunotherapeutic strategy against CHB, since CpG-C ODNs stimulate both B cell and dendritic cell (DC) activation. However, the efficacy of CpG-C ODN as an anti-HBV vaccine adjuvant remains unclear. In this study, we demonstrated that CpG M362 (CpG-C ODN) as an adjuvant in anti-HBV vaccine (cHBV-vaccine) successfully and safely eliminated the virus in HBV-carrier mice. The cHBV-vaccine enhanced DC maturation both in vivo and in vitro, overcame immune tolerance, and recovered exhausted T cells in HBV-carrier mice. Furthermore, the cHBV-vaccine elicited robust hepatic HBV-specific CD8⁺ and CD4⁺ T cell responses, with increased cellular proliferation and IFN-γ secretion. Additionally, the cHBV-vaccine invoked a long-lasting follicular CXCR5⁺ CD8⁺ T cell response following HBV re-challenge. Taken together, CpG M362 in combination with rHBVvac cleared persistent HBV and achieved long-term virological control, making it a promising candidate for treating CHB.     

Adjuvant properties of listeriolysin O protein in a DNA vaccination strategy

The use of infectious agents as vaccine adjuvants has shown utility in both prophylactic and therapeutic vaccinations. Listeria monocytogenes has been used extensively as a vaccine vehicle due to its ability to initiate both CD4⁺ and CD8⁺ immune responses. Previous work from this laboratory has used transgenic Listeria to deliver vaccine constructs. A chimeric protein composed of tumor antigen and a non-hemolytic variant of the Listeria protein, listeriolysin O (LLO), has demonstrated effective tumor protection beyond that of antigen alone expressed in the same system. To address the question of how fusion with LLO improves vaccine efficacy, we constructed a number of DNA plasmid vaccines to isolate this effect in the absence of other endogenous Listeria effects. Here we have analyzed the ability of these vaccines to induce the regression of previously established tumors. A vaccine strategy using DNA vaccines bearing the tumor antigen either alone or in combination with LLO in addition to plasmids encoding MIP-1α and GM-CSF was examined. Further, LLO was used either as a chimera or in a bicistronic construct to address the importance of fusion between these elements. Notably, the strategies employing both chimeric and bicistronic vaccines were effective in reducing tumor burden suggesting that LLO can act as an adjuvant that does not require fusion with the tumor antigen to mediate its effect.     

Combined TLR7/8 and TLR9 Ligands Potentiate the Activity of a Schistosoma japonicum DNA Vaccine

Background

Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX1-Sj26GST).

Methodology/Principal Findings

In this study, we evaluated a TLR7/8 ligand (R848) and a TLR9 ligand (CpG oligodeoxynucleotides, or CpG) as adjuvants for pVAX1-Sj26GST and assessed their effects on the immune system and protection against S. japonicum. We show that combining CpG and R848 with pVAX1-Sj26GST immunization significantly increases splenocyte proliferation and IgG and IgG2a levels, decreases CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Treg) frequency in vivo, and enhances protection against S. japonicum. CpG and R848 inhibited Treg-mediated immunosuppression, upregulated the production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-10, IL-2, and IL-6, and decreased Foxp3 expression in vitro, which may contribute to prevent Treg suppression and conversion during vaccination and allow expansion of antigen-specific T cells against pathogens.

Conclusions

Our data shows that selective TLR ligands can increase the protective efficacy of DNA vaccines against schistosomiasis, potentially through combined antagonism of Treg-mediated immunosuppression and conversion.     

Apoptosis of CD4<Superscript>+</Superscript>CD25<Superscript>high</Superscript> T cells in response to Sirolimus requires activation of T cell receptor and is modulated by IL-2

Targeted molecular therapies inhibit proliferation and survival of cancer cells but may also affect immune cells. We have evaluated the effects of Sirolimus and Sorafenib on proliferation and survival of lymphoid cell subsets. Both drugs were cytotoxic to CD4⁺CD25^high T cells, and were growth inhibitory for CD4⁺ and CD8⁺ T cells. Cytotoxicity depended on CD3/CD28 stimulation and was detectable within 12 h, with 80–90% of CD4⁺CD25^high cells killed by 72 h. Cell death was due to apoptosis, based on Annexin V and 7AAD staining. Addition of IL-2 prevented the apoptotic response to Sirolimus, potentially accounting for reports that Sirolimus can enhance proliferation of CD4⁺CD25^high cells. These results predict that Sirolimus or Sorafenib would reduce CD4⁺CD25^high cells if administered prior to antigenic stimulation in an immunotherapy protocol. However, administration of IL-2 protects CD4⁺CD25^high T cells from cytotoxic effects of Sirolimus, a response that may be considered in design of therapeutic protocols.     

Vaccine potential of hemocyanin from Oncomelania hupensis against Schistosoma japonicum

Hemocyanin, a giant oxygen transport protein which is usually found in many arthropods and mollusks was isolated and purified from Oncomelania hupensis. In this study, we showed that Oncomelania hupensis hemocyanin (OhH) shared carbohydrate epitopes with different developmental stages of Schistosoma japonicum (Cercaria, Schistosomulum, Adult worm and Egg) and exhibited serological cross-reaction with these stages of S. japonicum immune sera, which had a potential for use in diagnostic and therapeutic studies of schistosomasis. OhH was used as a vaccine in combination with Freund's adjuvant to evaluate the induction of immune responses and protection against S. japonicum infection in mice. Mice immunized with OhH induced a Th1 type of immune responses. Strong protection against S. japonicum were observed in adult worm and egg burdens after 42 days post-challenge, which showed a significant worm reduction of 52.5% and egg reduction of 69.2% compared to the control groups, respectively. These results indicated that OhH was a potential candidate to compose an anti-schistosome vaccine.     

CD8CD25 T cells reduce atherosclerosis in apoE(−/−) mice

Background

It is increasingly evident that CD8⁺ T cells are involved in atherosclerosis but the specific subtypes have yet to be defined. CD8⁺CD25⁺ T cells exert suppressive effects on immune signaling and modulate experimental autoimmune disorders but their role in atherosclerosis remains to be determined. The phenotype and functional role of CD8⁺CD25⁺ T cells in experimental atherosclerosis were investigated in this study.

Methods and results

CD8⁺CD25⁺ T cells were observed in atherosclerotic plaques of apoE(−/−) mice fed hypercholesterolemic diet. Characterization by flow cytometric analysis and functional evaluation using a CFSE-based proliferation assays revealed a suppressive phenotype and function of splenic CD8⁺CD25⁺ T cells from apoE(−/−) mice. Depletion of CD8⁺CD25⁺ from total CD8⁺ T cells rendered higher cytolytic activity of the remaining CD8⁺CD25⁻ T cells. Adoptive transfer of CD8⁺CD25⁺ T cells into apoE(−/−) mice suppressed the proliferation of splenic CD4⁺ T cells and significantly reduced atherosclerosis in recipient mice.

Conclusions

Our study has identified an athero-protective role for CD8⁺CD25⁺ T cells in experimental atherosclerosis.     

Heterogeneity of eosinophil chemotactic factors produced by splenic T cells of Schistosoma japonicum-infected mice

Spleen cells of Schistosoma japonicum-infected mice produced eosinophil chemotactic factors (ECF-Ls) upon stimulation with soluble egg antigen preparation (SEA) and Con A, while spleen cells from uninfected mice produced ECF-L upon stimulation with Con A but not with SEA. Depletion of CD4⁺ T cells, but not of CD8⁺ T cells, almost completely removed Con A-induced ECF-L production. In contrast, depletion of CD8⁺ T cells completely abolished SEA-induced ECF-L production while depletion of CD4⁺ T cells did not, indicating that CD4⁺ CD8⁻ T cells and CD4⁻CD8⁺ T cells play essential roles for the production of Con A-induced ECF-L and SEA-induced ECF-L, respectively. Con-A-induced ECF-L had a high affinity to Con A-Sepharose but not to Procion Red agarose. In contrast, SEA-induced ECF-L bound to Procion Red agarose, but not to Con A-Sepharose. A gel permission HPLC analysis revealed that the apparent molecular weight of Con A-induced ECF-L and SEA-induced ECF-L was 16 kDa and 35 kDa, respectively. Both Con A-induced ECF-L and SEA-induced ECF-L had a similar isoelectric point (pI 3.5–3.6). These results indicate that selective stimulation of either CD4⁺ or CD8⁺ T cells of S. japonicum-infected mice produces heterogeneous ECF-L.     

T cell precursor frequency differentially affects CTL responses under different immune conditions

Generation of effective CTL responses is the goal of many vaccination protocols. However, to what extant T cell precursor frequencies will generate a CD8⁺ CTL response has not been elucidated properly. In this study, we employed a model system, in which naive CD4⁺ and CD8⁺ T cells derived from ovalbumin (OVA)-specific TCR transgenic OT II and OT I mice were used for adoptive transfer into wild-type, Ia^b−/− gene knockout and transgenic RIP-mOVA mice, and assessed OVA-pulsed DC (DC_OVA)-stimulated CD8⁺ CTL responses in these mice. We demonstrated that (i) a critical threshold exists above which T cells precursor frequency cannot enhance the CTL responses in wild-type C57BL/6 mice, (ii) increasing CD8⁺ T cell precursors is required to generate CTL responses but with functional memory defect in absence of CD4⁺ T cell help, and (iii) increasing CD4⁺ and CD8⁺ T cell precursors overcomes immune suppression to DC_OVA-stimulated CD8⁺ CTL responses in transgenic RIP-mOVA mice with OVA-specific self immune tolerance. Taken together, these findings may have important implications for optimizing immunotherapy against cancer.     

狼疮性肾炎患者血清NETs、TWEAK、外周血CD4+T/CD8+T比例与疾病活动度及肾脏预后的关系

摘要 目的：探讨狼疮性肾炎（LN）患者血清中性粒细胞胞外诱捕网（NETs）、肿瘤坏死因子样凋亡微弱诱导剂（TWEAK）、外周血分化簇（CD）4⁺T/CD8⁺T比例与疾病活动度及肾脏预后的关系。方法：选取2021年8月～2022年8月川北医学院附属医院肾内科收治的LN患者137例（LN组）,根据系统性红斑狼疮疾病活动指数（SLEDAI）-2000评分分为轻度活动组（52例）、中度活动组（45例）、重度活动组（40例）。随访1年,根据肾脏相关终点事件发生情况分为预后不良组（43例）和预后良好组（94例）,另选取同期76名体检健康志愿者（对照组）。采用酶联免疫吸附法检测血清NETs、TWEAK水平,流式细胞术检测外周血CD4⁺T/CD8⁺T比例。Spearman相关性分析LN患者血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T与SLEDAI-2000评分的相关性,多因素Logistic回归分析LN患者预后不良的因素,受试者工作特征曲线分析血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T对LN患者预后不良的预测价值。结果：与对照组比较,LN组血清NETs、TWEAK水平升高,外周血CD4⁺T/CD8⁺T降低（P＜0.05）。轻度活动组、中度活动组、重度活动组血清NETs、TWEAK依次升高,外周血CD4⁺T/CD8⁺T依次降低（P＜0.05）。LN患者SLEDAI-2000评分与血清NETs、TWEAK呈正相关,与外周血CD4⁺T/CD8⁺T呈负相关（P＜0.05）。慢性肾脏病分期4期、SLEDAI-2000评分升高、NETs升高、TWEAK升高为LN患者预后不良的独立危险因素,估算肾小球滤过率升高、CD4⁺T/CD8⁺T升高为独立保护因素（P＜0.05）。血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T联合预测LN患者预后不良的曲线下面积为0.943,大于血清NETs、TWEAK和外周血CD4⁺T/CD8⁺T单独预测的0.790、0.788、0.799（P＜0.05）。结论：LN患者血清NETs、TWEAK水平升高,外周血CD4⁺T/CD8⁺T降低,与疾病活动度及肾脏预后不良密切相关,血清NETs、TWEAK联合外周血CD4⁺T/CD8⁺T预测LN患者肾脏预后的价值较高。