真性红细胞增多症患者T细胞的克隆特点

目的　了解真性红细胞增多症（ＰＶ）患者外周血Ｔ细胞受体（ＴＣＲ）Ｖβ２４ 个亚家族基因的表达及其克隆特点。方法　采用逆转录多聚酶链反应（ＲＴＰＣＲ） 检测３ 例ＰＶ 患者外周血单个核细胞ＴＣＲＶβ２４ 个亚家族基因表达情况;采用基因扫描分析Ｔ细胞的克隆特点。结果　３ 例ＰＶ患者外周血仅表达４ ～１４ 个Ｖβ亚家族,主要为Ｖβ２ 、Ｖβ３ 、Ｖβ１６ 、Ｖβ２１ 和Ｖβ２３ ;２ 例患者表达的Ｖβ３ 和Ｖβ２３Ｔ细胞为克隆性增殖。结论　ＰＶ 患者外周血ＴＣＲＶβ亚家族的优势表达和克隆性增殖可能是患者体内对抗恶性细胞的免疫反应特征。     

急性髓系白血病患者外周血T细胞TCR Vβ亚家族表达及克隆性增殖分析

本研究探讨AML患者在初发、治疗缓解后、复发等不同疾病状态下外周血T细胞TCRVB亚家族表达及T细胞克隆性增殖的情况,分析不同白血病细胞负荷对患者外周血T淋巴细胞数量及功能．尤其是对抗白血病功能的影响。应用RT-PCR扩增11例AML白血病患者不同疾病状态下及3名正常供者外周血的TCRBV24个家族的基因序列,通过基因扫描（genescan）的方法判断TCRBV家族的克隆表达、CDR3克隆性质,比较不同疾病状态下白血病患者外周血T细胞的Vβ亚家族的应用、克隆性增殖、T细胞的复杂性以及T细胞免疫表型的变化。结果表明：11例AML白血病患者初诊时外周血T细胞均表达部分TCR Vβ亚家族,经体外诱导后TCR Vβ亚家族表达增加;完全缓解期患者外周血T细胞TCRVβ亚家族数量明显增多,但未达到完全正常;4例患者在复发时TCR Vβ亚家族表达数量明显下降;11例患者中有9例在初诊时外周血有1至2个TCR Vβ亚家族T细胞克隆性增殖,缓解期克隆性增殖的Vβ亚家族T细胞有增加趋势,在多数病例观察到部分Vβ亚家族T细胞在初发、缓解、体外诱导扩增以及复发时仍维持克隆性增殖状态;AML白血病患者初发及复发时T细胞CDR3复杂性明显降低,呈偏态分布,而疾病缓解时T细胞复杂性有所改善。结论：AML白血病患者外周血T细胞TCR Vβ亚家族呈限制性表达;在大多数病例中无论是疾病初发抑或缓解及体外诱导、甚至在疾病复发时均可观察到克隆性T细胞的存在;在部分病例中某些Vβ亚家族在上述不同疾病状态下始终维持克隆性增殖状态,部分Vβ亚家族的克隆性增殖同白血病细胞的存在相关;在疾病状态下,AML白血病患者外周血T细胞的复杂性有所降低,而疾病缓解后可部分恢复。     

Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage.

We have investigated the T cell receptor V alpha and V beta gene family usage by T lymphocytes infiltrating affected thyroids in patients with autoimmune thyroid disease. We show that the intrathyroidal T lymphocytes from patients (n = 6) with autoimmune thyroid disease display a widespread usage of V beta gene families with an average of 14.4/19 V beta gene families similar to the peripheral T lymphocytes of the same patients. Because we recently reported that the utilization of V alpha gene families is markedly reduced within these mitogen-stimulated intrathyroidal T cell populations, as well as within intact tissue from similar patients (n = 4) (overall mean of 4.0/18 families detected), these results indicate that in thyroids of patients with autoimmune thyroid disease the lymphocytes are selectively accumulating based on their V alpha rather than V beta elements. This preferential hTcR V alpha and widespread V beta gene usage was not mimicked in most 7-d autologous mixed lymphocyte reactions using non-T cell stimulators (n = 6) or EB-virus immortalized autologous B cell lines (n = 3). Hence, the selective V gene utilization by intrathyroidal T cells is likely to be secondary to multiepitopic thyroidal autoantigens activating thyroid infiltrating T cells or to the presence of a superantigenlike thyroidal self-antigen, capable of determining a selective infiltration or activation of a variety of T lymphocytes on the basis of their V alpha gene usage.     

Repression of B7.2 on Self-reactive B Cells Is Essential to Prevent Proliferation and Allow Fas-mediated Deletion by CD4+ T Cells

Peripheral tolerance mechanisms normally prevent delivery of T cell help to anergic self-reactive B cells that accumulate in the T zones of spleen and lymph nodes. Chronic exposure to self-antigens desensitizes B cell antigen receptor (BCR) signaling on anergic B cells so that they are not stimulated into clonal expansion by CD4⁺ T cells but instead are eliminated by Fas (CD95)-induced apoptosis. Because a range of BCR-induced signals and responses are repressed in anergic B cells, it is not known which of these are critical to regulate for Fas-mediated peripheral tolerance. Display of the costimulatory molecule, B7.2 (CD86), represents a potentially important early response to acute BCR engagement that is poorly induced by antigen on anergic B cells. We show here that restoring B7.2 expression on tolerant B cells using a constitutively expressed B7.2 transgene is sufficient to prevent Fas-mediated deletion and to trigger extensive T cell–dependent clonal expansion and autoantibody secretion in the presence of specific T cells. Dysregulated expression of B7.2 on tolerant B cells caused a more extreme reversal of peripheral tolerance than that caused by defects in Fas or Fas ligand, and resulted in T cell–dependent clonal expansion and antibody secretion comparable in magnitude to that made by foreign antigen-specific B cells. These findings demonstrate that repression of B7.2 is critical to eliminate autoreactive B cells by Fas in B cell–T cell interactions. The possible role of B7.2 dysregulation in systemic autoimmune diseases is discussed.     

Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity

The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell-depleting therapies for autoimmune diseases.     

Anergy in peripheral memory CD4(+) T cells induced by low avidity engagement of T cell receptor

Induction of tolerance in self-reactive memory T cells is an important process in the prevention of autoimmune responses against peripheral self-antigens in autoimmune diseases. Although naive T cells can readily be tolerized, memory T cells are less susceptible to tolerance induction. Recently, we demonstrated that low avidity engagement of T cell receptor (TCR) by low densities of agonist peptides induced anergy in T cell clones. Since memory T cells are more responsive to lower antigenic stimulation, we hypothesized that a low avidity TCR engagement may induce tolerance in memory T cells. We have explored two antigenic systems in two transgenic mouse models, and have tracked specific T cells that are primed and show memory phenotype. We demonstrate that memory CD4(+) T cells can be rendered anergic by presentation of low densities of agonist peptide-major histocompatibility complex complexes in vivo. We rule out other commonly accepted mechanisms for induction of T cell tolerance in vivo, such as deletion, ignorance, or immunosuppression. Anergy is the most likely mechanism because addition of interleukin 2-reversed anergy in specific T cells. Moreover, cytotoxic T lymphocyte antigen (CTLA)-4 plays a critical role in the induction of anergy because we observed that there was increased surface expression of CTLA-4 on anergized T cells, and that injection of anti-CTLA-4 blocking antibody restored anergy in vivo.     

Oligoclonal Expansions of CD8+ T Cells in Chronic HIV Infection Are Antigen Specific

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8⁺ T cells. These ‘expansions'', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8⁺ T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex–peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain–specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8⁺ T cells are HIV specific in vivo.     

慢性粒细胞白血病患者外周血初始T细胞水平和T细胞受体Vβ谱系利用特点

目的了解慢性粒细胞白血病(CML)患者外周血初始(naive)T细胞的水平和T细胞受体(TCR)Vβ基因谱系利用和克隆性,从而了解CML患者的胸腺近期输出功能和TCRVβ亚家族T细胞增殖情况。方法采用实时定量PCR(TaqMan)方法检测20例CML患者外周血单个核细胞中T细胞受体重排删除环(Tcellreceptorrearrangementexcisioncircles,TREC)的水平,并根据外周血中CD3阳性率计算CD3+细胞中TREC水平。利用逆转录PCR和基因扫描分析其中14例患者外周血单个核细胞的TCRVβ24个亚家族基因表达和克隆性。9名正常人外周血作为对照。结果CML患者外周血TREC含量(0.06±0.16/1000CD3+细胞)明显低于正常人(6.84±4.71/1000CD3+细胞,P<0.01)。14例CML患者外周血T细胞表达不同数量Vβ亚家族(1～12个),其中13例CML患者外周血中的一些Vβ亚家族出现克隆性T细胞,Vβ3,Vβ10,Vβ19,Vβ21和Vβ22亚家族的克隆性增殖多见。结论CML患者胸腺近期输出初始T细胞功能明显降低,但仍存在优势利用和克隆性增殖Vβ亚家族T细胞,提示尽管整体T细胞免疫功能低下,但对白血病细胞相关抗原仍具有一定特异性免疫反应的能力。     

新型调节性T细胞：iTR35

调节性T细胞是不同于Th1和Th2的具有调节功能的T细胞群体，因其具有免疫抑制功能，在多种免疫性疾病中起重要的调节作用，近年日益受到人们的广泛关注。最近的研究证明IL-35能够诱导生成一种新型调节性T细胞，这种新型调节性T细胞通过分泌IL-35和IL-10起免疫抑制功能，称为“iTr35”。与TGF-β诱导的iTreg不同，iTr35不表达Foxp3，其功能的维持也与Foxp3无关。更为重要的是，与TGF-β诱导的iTreg相比，iTr35在体内非常稳定，因此人们推测iTr35在感染耐受的形成中起重要的作用。     

Failure of clonal deletion in neonatally thymectomized mice: tolerance is preserved through clonal anergy

Self-tolerance is achieved in part through intrathymic deletion of self-reactive T cells. The necessity of the thymus for this process is suggested by the development of autoimmune diseases in neonatally thymectomized (neoTx) mice and by the failure of clonal deletion in nude mice. Indeed, the present study demonstrates that neonatal thymectomy on day 3 after birth results in the failure of clonal deletion of V beta 11+ T cells in BALB/c mice and V beta 5+ and V beta 6+ T cells in DBA/2 mice. However, these potentially autoreactive cells are nonfunctional as measured by proliferation and lymphokine production after stimulation with appropriate anti-V beta mAbs or stimulator cells. It appears that this induction of nonresponsiveness may have occurred extrathymically: the early neonatal thymus (presumably the source of the peripheral T cells observed in neoTx mice) also contains T cells with self-reactive receptors, but these cells are fully functional. Therefore, neonatal thymectomy aborts deletion of self-reactive T cells, but self-tolerance is maintained through functional inactivation of potentially self-reactive clones.     

乙型肝炎病毒感染者CD8^＋T淋巴细胞T细胞抗原受体Vβ基因互补决定区3克隆化特征的研究

目的研究乙型肝炎病毒感染者CD8^＋T淋巴细胞T细胞抗原受体（TCR）Vβ基因互补决定区3（CDR3）克隆化特征。方法选用20例乙型肝炎感染者及20例同期健康体检者,应用多引物聚合酶链反应（PCR）方法同时扩增TCRVβ基因CDR3区多个片段,高分辨率琼脂糖凝胶电泳检测克隆化特征。结果乙型肝炎病毒感染者CD8^＋T细胞TCR Vβ9和Vβ14克隆化明显高于正常对照组,分别为70．0％vs 25．0％、85．0％vs 30．0％（P〈0．01）。结论乙型肝炎病毒感染者存在CD8^＋T细胞TCR Vβ9和Vβ14克隆性变化。     

Direct evidence for thymic function in adult humans.

The understanding of human thymic function and evaluation of its contribution to T cell homeostasis are matters of great importance. Here we report the development of a novel assay to quantitate the frequency and diversity of recent thymic emigrants (RTEs) in the peripheral blood of humans. Such cells were defined by the presence of T cell receptor (TCR) rearrangement deletion circles (DCs), episomal byproducts of TCR-beta V(D)J rearrangement. DCs were detected in T cells in the thymus, cord blood, and adult peripheral blood. In the peripheral blood of adults aged 22 to 76 years, their frequency was highest in the CD4(+)CD45RA(+) CD62L(+) subpopulation of naive T cells. TCR DCs were also observed in other subpopulations of peripheral blood T cells, including those with the CD4(+)CD45RO(-)CD62L(+) and CD4(+)CD45RO(+)CD62L(+) phenotypes. RTEs were observed to have more than one Vbeta rearrangement, suggesting that replenishment of the repertoire in the adult is at least oligoclonal. These results demonstrate that the normal adult thymus continues to contribute, even in older individuals, a diverse set of new T cells to the peripheral circulation.     

多发性硬化患者T细胞克隆中CD3CD56双阳性细胞的分析

目的多发性硬化(MS)是一种器官特异的自身免疫病,病变侵犯中枢神经系统.MS不仅有T,B细胞介导,而且与脑淋巴瘤的发生有密切关系.方法本文用T细胞克隆技术,细胞表型分析技术和细胞毒活性分析经MBP抗原肽治疗的MS患者外周血的T,B淋巴细胞(另文发表).结果经MBP抗原肽诱导的T细胞克隆中有相当一部分T细胞系不仅高表达CD3CD56双阳性标志(NKT细胞),50.7%±4.9%,对照为6.0%和3.0%,而其他神经系统疾病分别是11.0%和20.0%,且这种双阳性细胞群不同于NK细胞能特异杀伤神经胶质瘤(59.7%±4.9%)而NK细胞仅为17.3%±4.5%,具有统计学差异.结论用MBP抗原肽诱导的T细胞克隆可用作疫苗治疗MS患者,而这种高表达CD3CD56双阳性标志(NKT细胞)对神经胶质瘤细胞较NK细胞潜在的更强的杀伤活性.至于其抗瘤机制正在研究之中.     

Perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive T cells

A number of in vitro studies have suggested that costimulatory molecules B7-1 and B7-2 and their receptor CD28 can promote clonal deletion, and limited in vivo studies have indicated that CD28 is involved in the clonal deletion of some T cells. However, the significance of B7-mediated clonal deletion in preventing autoimmune diseases has not been studied systematically. Here we report that the perinatal blockade of B7-1 and B7-2 substantially inhibits the clonal deletion of T cells in the thymus and leads to an accumulation of T cells capable of inducing fatal multiorgan inflammation. These results reveal a critical role for costimulatory molecules B7-1 and B7-2 in deleting pathogenic autoreactive T cells in the thymus. The critical role of B7-1 and B7-2 in T cell clonal deletion may explain, at least in part, the paradoxical increase of autoimmune disease in mice deficient for this family of costimulatory molecules, such as cytotoxic T lymphocyte associated molecule 4, CD28, and B7-2. The strong pathogenicity of the self-reactive T cells supports a central hypothesis in immunology, which is that clonal deletion plays an important role in preventing autoimmune diseases.     

Complementarity-determining region 3 size spectratypes of T cell receptor beta chains in CD8+ T cells following antiviral treatment of chronic hepatitis B

An increased CD8(+) T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8(+) T cells at these time points predict the virological response to therapy. Peripheral blood CD8(+) T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) β chain variable region (Vβ) gene family was analyzed, and the changes in the numbers of Vβ families with clonal expansions were compared in subjects with (n = 12) and without (n = 8) a virological response (52 week HBV DNA < 300 copies/ml). The number of CD8(+) TCR Vβ families with clonal expansions at 12 weeks relative to baseline (median [10th to 90th percentile], +2.5 [0 to +7] versus +1 [0 to +2], P = 0.03) and at 24 weeks relative to 12 weeks (+1 [0 to +2] versus -1 [-3 to +4], P = 0.006) was higher in subjects with a virological response versus subjects without a virological response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P < 0.0001) in responders. Increased numbers of CD8(+) T cell expansions after antiviral therapy are associated with a virological response to treatment. These CD8(+) T cells are a potential target for a therapeutic vaccine for chronic hepatitis B.     

Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.     

Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis.

Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4+ T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4+ populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1*04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for V beta 3+, V beta 14+, and V beta 17+CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V beta 17+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation. The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint.     

间充质干细胞的免疫调节功能及间充质干细胞在治疗自身免疫疾病中的应用

间充质干细胞（MSC）是一类可从多类成体组织中分离的能向脂肪细胞、成骨细胞和软骨细胞等分化的成体干细胞,是组织工程细胞的一个理想来源。它能够与免疫系统相互作用,抑制T细胞、B细胞和NK细胞的功能,影响DC的活性。输入体内后,MSC可诱导外周免疫耐受并且可迁移到受损组织,抑制促炎症因子表达,促进受损细胞的存活。近年来MSC应用于对移植物抗宿主疾病（GVHD）的治疗,很好的降低了GVHD发生率和进程。MSC的这种免疫调节作用对治疗自身免疫疾病应该有良好的应用前景。本文主要综述MSC的免疫调节机制和MSC对自身免疫疾病的治疗进展。     

Heterogeneity of autoreactive T cell clones specific for the E2 component of the pyruvate dehydrogenase complex in primary biliary cirrhosis

The extraordinary specificity of bile duct destruction in primary biliary cirrhosis (PBC) and the presence of T cell infiltrates in the portal tracts have suggested that biliary epithelial cells are the targets of an autoimmune response. The immunodominant antimitochondrial response in patients with PBC is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). Hitherto, there have only been limited reports on the characterization and V beta usage of PDC-E2-specific cloned T cell lines. In this study, we examined peripheral blood mononuclear cells (PBMC) for their reactivity to the entire PDC complex as well as to the E1- and E2-specific components. We also examined the phenotype, lymphokine profile, and V beta usage of PDC-specific T cell clones isolated from cellular infiltrates from the livers of PBC patients. We report that PBMC from 16/19 patients with PBC, but not 12 control patients, respond to the PDC-E2 subunit. Interestingly, this response was directed to the inner and/or the outer lipoyl domains, despite the serologic observation that the autoantibody response is directed predominantly to the inner lipoyl domain. Additionally, lymphokine analysis of interleukin (IL) 2/IL-4/interferon gamma production from individual liver-derived autoantigen-specific T cell clones suggests that both T helper cell Th1- and Th2-like clones are present in the liver. Moreover, there was considerable heterogeneity in the T cell receptor for antigen (TCR) V beta usage of these antigen- specific autoreactive T cell clones. This is in contrast to murine studies in which animals are induced to develop autoimmunity by specific immunization and have an extremely limited T cell V beta repertoire. Thus, our data suggest that in human organ-specific autoimmune diseases, such as PBC, the TCR V beta repertoire is heterogenous.     

原发性胆汁性肝硬化患者肝硬化期外周血淋巴细胞计数及T细胞亚群检测与分析

目的探讨原发性胆汁性肝硬化(PBC)患者肝硬化期外周血淋巴细胞总数及T细胞亚群的特点并分析影响因素及临床意义。方法对86例肝硬化期PBC患者的临床资料、实验诊断数据进行回顾性分析,比较40例代偿期和46例失代偿期PBC患者肝功、免疫学指标和外周血淋巴细胞亚群特点,对可能的影响因素进行相关性分析。结果失代偿期PBC患者年龄、血清总胆红素(TBil)水平、血清总IgA水平、Mayo评分高于代偿期患者(P0.05),而ALT、ALB、外周血淋巴细胞绝对数(LYMPH)、淋巴细胞百分率(LYMPH%)、T淋巴细胞绝对数(CD3+)、T辅助细胞绝对数(CD3+CD4+)和T抑制细胞绝对数(CD3+CD8+)均低于代偿期患者(P0.05);LYMPH、LYMPH%、CD3+、CD3+CD4+和CD3+CD8+结果中,失代偿期减低者频率均高于代偿期(45.7%vs.10%,34.8%vs.7.5%,58.7%vs.17.5%,45.7%vs.5%,60.9%vs.27.5%,P0.05),失代偿期增高者频率均低于代偿期(54.3%vs.90%,6.5%vs.27.5%,0 vs.20%,2.2%vs.22.5%,2.2%vs.10%,P0.05)。在可能的影响因素中,年龄、Mayo评分、上消化道出血、脾大或脾切除、腹水等肝硬化失代偿表现对结果影响呈负相关;而ALT、ALB对结果影响呈正相关。结论随着肝硬化程度的加深,PBC患者外周血淋巴细胞总数及T细胞亚群数量降低;从淋巴细胞定量角度分析,随着疾病的进展,PBC患者免疫水平下降。