自身免疫性甲状腺疾病和亚急性甲状腺炎树突状细胞与HLA-DR抗原表达观察

目的：探讨树突状细胞（DC）和HLA－DR抗原表达在Graves病（GD）,桥本甲状腺炎（HT）和亚急性甲状腺炎（SAT）发病中的作用。方法：用组织化学、免疫组织化学方法观察有明显淋巴细胞浸润的GD53例,HT52例和SAT31例甲状腺实质和间质中DC和HLA－DR抗原表达的免疫活性细胞和甲状腺滤泡上皮细胞的病理形态学变化,并结合形态计量学方法,进一步探讨他们与GD、HT和SAT病理学分型,临床症状,体征及与自身免疫性甲状腺疾病和SAT发生,发展的关系。结果：GD、HT各型和SAT不同病变区中S－100阳性DC和HLA－DR抗原表达的甲状腺滤泡上皮细胞随着润程度的进展逐渐增加。在HT的O－型和SAT的肉芽肿区达最高峰,HT的P－型和SAT的明显纤维化区则明显减少,而HLA－DR抗原表达的免疫活性细胞数量却为最高峰。DC和HLA－DR抗原表达的免疫活性细胞分布在甲状腺滤泡间,滤泡上皮细胞间并与弥漫浸润的淋巴细胞,浆细胞,巨噬细胞等相混杂,有些还分布在淋巴滤泡或肉芽肿中,并与相邻细胞密切接触,结论：本研究结果提示DC和HLA－DR抗原阳性细胞共同协调发挥的甲状腺自身抗原递呈作用和直接杀伤的细胞毒作用在GD、HT和SAT发生,发展的免疫发病机制中可能存在着一定的联系。     

免疫原性和耐受性树突状细胞在粥样硬化动脉壁内的分布及意义

目的　研究免疫原性和耐受性血管树突状细胞在下肢动脉硬化闭塞症动脉壁内的分布情况,探讨免疫原性和耐受性血管树突状细胞与下肢动脉硬化闭塞症之间的关系。方法　人下肢动脉标本40例主要取自尸检和外科手术,常规石蜡切片,10例下肢动脉内膜形态结构未见明显改变的设为对照组,30例下肢动脉病变较明显的设为实验组;免疫组织化学染色观察人S100蛋白阳性、免疫原性CD1a、CD83、趋化因子受体7（CCR7）阳性和耐受性CD11b、树突状细胞特异性细胞间黏附分子3-结合非整合素分子（DC-SIGN）、Toll样受体2（TLR-2）、吲哚胺2,3双加氧酶（IDO）阳性反应血管树突状细胞的分布;免疫印迹法检测免疫原性和耐受性血管树突状细胞标志物的表达。结果　实验组大量表达人S100蛋白、CD1a、CD83和CCR7阳性血管树突状细胞,且主要分布在内膜斑块处和外膜小血管周围,数量较多,中膜内有少量阳性细胞分布,实验组少量表达CD11b、DC-SIGN、TLR-2、IDO阳性血管树突状细胞,且主要分布在内膜斑块处和外膜小血管周围,数量较少,中膜内有少量阳性细胞分布;免疫印迹结果发现实验组高表达CD1a和CD83,且较少表达CD11b和IDO。结论　免疫原性及耐受性血管树突状细胞在动脉粥样硬化闭塞症病变动脉内膜中聚集且免疫原性血管树突状细胞含量明显高于耐受性血管树突状细胞,提示免疫原性血管树突状细胞可能参与了动脉粥样硬化闭塞症的形成过程并且免疫原性血管树突状细胞的增高可能参与了动脉粥样硬化闭塞症的炎症性免疫反应。     

急性髓系白血病细胞诱导分化生成树突状细胞的研究

目的　将急性髓系白血病 (AML)原代细胞诱导成树突状细胞 (DC) ,并探索白血病免疫治疗的新途径。方法　分离初诊AML患者 12例和正常人 6例的骨髓单个核细胞 ,用重组人粒单核细胞集落刺激因子 (rhGM CSF) 10 0 0U /ml、重组人白细胞介素 4(rhIL 4) 50 0U/ml和肿瘤坏死因子α(TNF α) 50U/ml联合培养 10d ;经形态学 (Wright染色、倒置显微镜、透射电镜 ) ,免疫学 (CD80 、CD86 、CD83 、CD1a、HLA DR)鉴定 ,荧光原位杂交 (FISH)进行细胞遗传学分析 ,混合淋巴细胞反应检测功能。结果　细胞因子联合诱导后 ,呈现DC的典型形态 ,CD80 、CD86 、CD83 、CD1a的表达与对照组比较明显上调 (P <0 0 5) ,具有刺激T淋巴细胞增殖的能力。经FISH证实来源于白血病细胞的这类DC与正常DC在形态和免疫学表达方面相似 (P >0 0 5) ,但功能较弱。结论　在体外可成功的将AML原代细胞诱导分化成DC ,可望用于AML的免疫治疗     

人脐血和外周血树突状细胞诱导抗肝癌活性

目的　观察人脐血和外周血树突状细胞 (dendriticcells ,DC)的生物学特性及其对效应细胞体外杀伤人肝癌细胞株BEL 740 2 (B)的影响。方法　免疫组化和MTT法检测DC的生物学特性。抗肿瘤实验则分两大组 ,人外周血DC组为B +LAK +DC ,人脐血DC组为B +DC CTL ,检测效应细胞的细胞毒活性。结果　①人外周血和脐血DC均高表达HLA ABC、HLA DR、HLA DQ、CD54和S 10 0蛋白 ;刺激淋巴细胞增殖的效应均比对照组明显增高 (P <0 0 1) ,两种来源DC无显著性差异 (P >0 0 5)。②人外周血DC组和脐血DC组的细胞毒活性均为实验组 >对照组 (P <0 0 1) ,人脐血DC组 >人外周血DC组 (P <0 0 1)。结论　人外周血和脐血DC均为形态和功能成熟的DC ,均能明显增强效应细胞杀伤肝癌细胞的活性 ;而经肿瘤抗原致敏DC诱导的特异性CTL杀伤活性更强。提示临床上可根据患者的具体情况选择DC的来源     

乙型肝炎相关肝癌外周血树突状细胞负载肿瘤抗原前后免疫功能的变化

目的探讨肝癌患者外周血单个核细胞(PBMC)来源树突状细胞(DC)表面分子表达及负载肿瘤抗原前后免疫功能变化与免疫逃逸的关系。方法分离18例乙型肝炎相关原发性肝癌、11例乙型肝炎肝硬化患者和10名健康献血者PBMC,体外培养,并加入重组人粒细胞巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)诱导DC。以共聚焦显微镜和扫描电镜观察形态,以流式细胞仪检测DC表面人类白细胞抗原(HLA)-DR、CD1a、CD80、CD83、CD86等分子表达水平。以HCCLM6肝癌细胞株制备肿瘤抗原,分别负载3种DC,最后以混合淋巴细胞反应(MLR)测定DC负载前后刺激同种异型T淋巴细胞增殖能力,并测定MLR上清液中IL-12的含量。结果肝硬化和肝癌组PBMC、DC得率低于正常组(P<0.05);HLA- DR、CD1a、CD80和CD86等分子表达水平也低于正常组(P<0.05);负载肿瘤抗原前肝硬化和肝癌组刺激同种异型T淋巴细胞增殖能力和MLR上清液中IL-12含量明显低于正常组,负载肿瘤抗原后3组均提高, 并以肝硬化组提高最为明显,但IL-12含量仍低于正常组。结论DC表型和功能缺陷可能是乙型肝炎病毒产生免疫耐受和肝癌细胞免疫逃逸的重要机制。肝硬化患者DC仍有一定功能。     

慢性乙型肝炎树突状细胞表型和功能的变化与免疫耐受

目的 观察慢性乙型肝炎病毒（HBV）感染者树突状细胞（DC）形态和功能的改变。方法 从13例慢性乙型肝炎患者和11例健康人外周血中分离和培养DC,观察DC的形态,用流式细胞仪检测DC表面标记HLA－DR、CD1a、CD80和CD86的表达,用^3H-TdR掺入法测定DC诱导混合性淋巴细胞反应（MLR）的能力。结果 正常DC较慢性乙型肝炎患者在形态上更为典型,不规则,HLA－DR、CD80和CD86分子的表达水平较高（P＜0.05）,诱导MLR的能力较强（P＜0.05）。结论 慢性乙型肝炎患者外周血DC处于不完全成熟状态,其免疫刺激能力较低。     

急性髓细胞白血病细胞诱导分化成为树突状细胞的实验研究

目的 :探讨急性髓细胞白血病 (AML)患者的白血病细胞体外是否可诱导分化成为树突状细胞(DC)。方法 :从 11例AML患者的骨髓或外周血中获取非贴壁细胞 ,利用细胞因子 (rhGM CSF、rhIL 4、rhTNF α)联合培养 ,每 12d收获细胞。培养前后分别用倒置显微镜、电镜观察细胞形态 ,用流式细胞术测定细胞表面标志 ,用MTT法检测收获细胞激发混合淋巴细胞反应的能力。结果 :8例AML标本分化成为具有典型树突状形态的细胞 ,培养后的白血病细胞的HLA DR、CD86、CD1a表达较培养前明显增高 ,差异有统计学意义 (P <0 .0 1)。在混合淋巴细胞反应中 ,DC具有强烈激发同种T淋巴细胞增殖的能力 ,且随数量增加而作用增强。M4/M5型AML DC的表面标志的表达率明显高于非M4/M5型AML DC(P <0 .0 1)。结论 :急性髓细胞白血病细胞可以诱导分化成为具有DC形态、表型、功能的细胞。     

趋化素样因子1在类风湿关节炎滑膜中的表达研究

目的研究趋化素样因子1(CKLF1)在类风湿关节炎(RA)滑膜中的表达,探讨CKLF1在RA发病过程中的可能的病理作用。方法取35例RA,20例骨关节炎(OA)及20例半月板损伤患者手术切除的膝关节滑膜标本。采用反转录-聚合酶链反应(RT-PCR)方法检测CKLF1在上述3种病变滑膜中的mRNA水平表达水平。采用免疫组织化学方法检测CKLF1在滑膜组织中的蛋白水平表达特征。结果RA滑膜组织中CKLF1在mRNA水平的表达(0．41±0．17)明显高于OA(0．07±0．06)和半月板损伤患者(0．16±0．10)(P<0．05)。免疫组织化学结果显示,OA病例中仅有2例显示少量滑膜衬里层细胞着色,半月板损伤病例仅有5例显示少量滑膜衬里层细胞着色。在RA滑膜中20例染色强阳性,10例染色阳性,5例染色阴性。阳性染色颗粒位于细胞胞质内,阳性细胞定位在滑膜衬里层的成纤维细胞、滑膜下层大量的浆细胞以及增生的血管上皮细胞。结论CKLF1基因在RA滑膜中有高水平的表达特征,为进一步深入研究RA的发病机制提供新的研究思路。     

类风湿关节炎滑膜巨噬细胞来源的研究

目的　了解类风湿关节炎 (RA)滑膜巨噬细胞的来源。方法　采用免疫组化LSAB法对 2 6例RA滑膜 ,2 0例非RA滑膜及 7例正常滑膜进行连续切片CD6 8和PCNA染色。结果　正常滑膜衬里层细胞几乎全部CD6 8阳性而PCNA阴性 ,衬里下层CD6 8和PCNA阳性细胞极少 ;RA滑膜衬里层和衬里下层PCNA阳性细胞数较非RA滑膜明显增多 (P <0 0 5 ) ,衬里层滑膜细胞大部分CD6 8阳性 ,衬里下层CD6 8阳性细胞数较非RA滑膜明显增多 (P <0 0 5 ) ,并且衬里层和衬里下层部分CD6 8阳性的细胞PCNA也阳性。结论　RA滑膜增多的A型巨噬样滑膜细胞和衬里下层的巨噬细胞都有局部增生 ,表明RA滑膜衬里下层聚集的巨噬细胞除来源于血液中的单核细胞趋化转移外 ,还与巨噬细胞在炎症局部增生有关。     

胆囊癌组织中树突状细胞与PCNA表达及意义

研究胆囊组织中树突状细胞 (DC)浸润程度和增殖细胞核抗原 (PCNA)表达与浸润、转移的关系并探讨DC和PCNA表达的相关性。用免疫组化SP法检测 4 6例胆囊癌组织S - 10 0阳性标记的DC数量和PCNA表达。在胆囊癌中S - 10 0蛋白阳性的DC和PCNA阳性表达率分别为 5 2 2 %和 6 9 6 %。DC浸润与胆囊癌的浸润程度和淋巴结转移呈负相关 (P <0 0 5 ) ,PCNA表达与胆囊癌的浸润程度和淋巴结转移呈正相关 (P <0 0 5 ) ,DC与PCNA表达呈明显负相关 (P <0 0 5 )。DC和PCNA表达与胆囊癌的侵袭和淋巴结转移密切相关。     

Comparison of blood and synovial fluid lymphocyte subsets in rheumatoid arthritis and osteoarthritis

Summary Immunoregulatory T-cell deficiency is thought to underlie pathogenesis of rheumatoid arthritis (RA) as a systemic autoimmunopathy. The aim of this study was a simultaneous analysis of peripheral blood and synovial lymphocyte subsets (Ly-SS) of RA patients as compared to patients with locally active osteoarthritis (OA). Peripheral blood Ly-SS and paired synovial fluid Ly-SS from 87 RA patients were analysed by two dimensional flow cytometry (Simulset Becton Dickinson) as compared to 15 OA patients. The control group consisted of 32 healthy subjects. The peripheral blood analysis from RA and OA patients revealed a significant decrease of CD8+T-cells and increase of CD4+:CD8+ ratio when compared to the control group. The blood of RA patients showed a significant increase of HLA DR+ and IL 2R+T cells as compared to OA group. The synovial fluid from RA and OA patients showed a significant increase of CD3+, CD8+, HLA DR+ T-cells and decrease of CD4+:CD8+ ratio and CD19+ cells in comparison to the peripheral blood. This study shows, that the OA T-cell system seems not to be activated in peripheral blood in opposition to RA patients. Synovial fluid Ly-SS in OA, however, showed only quantitative but not qualitative differences. OA seems to be mainly a local inflammatory response depending on T-cells, when lymphocyte T activity in blood is diminished.     

Changes in CD4+ T Lymphocyte Subsets in Circulating Blood and Synovial Fluid Following Filtration Leukocytapheresis Therapy in Patients with Rheumatoid Arthritis

The purpose of this study is to determine the changes in CD4+ T lymphocyte subsets in the circulating blood and synovial fluid following filtration leukocytapheresis (LCP) therapy for patients with rheumatoid arthritis (RA). A Cellsorba column packed with polyester fibers was used for the removal of circulating leukocytes. For patients with RA, filtration LCP or sham procedures were performed 3 times with 1 week intervals between procedures. T lymphocyte surface markers in the peripheral blood and synovial fluid were measured by flow cytometry. The proportions of activated CD4+ T cells (CD4+DR+, CD4+CD25+, and CD4+CD71+) and CD4+CD29+ T cells increased significantly in the peripheral blood, but the counts of these cells were significantly reduced in the synovial fluid after 2 treatment sessions in the LCP group. No significant changes were observed in the proportion of these cells in the control group. Our findings suggest that filtration LCP may cause a redistribution of activated T cells from affected joints into the circulating blood.     

Increased percentage of cd3+, cd57+ lymphocytes in patients with rheumatoid arthritis. correlation with duration of disease

Objective. To determine whether a small CD3+ lymphocyte population expressing 110-kd CD57 antigens (HNK1) is expanded in patients with rheumatoid arthritis (RA), as it is in patients who have undergone bone marrow transplantation and patients with the acquired immunodeficiency syndrome, and to investigate whether it is involved in the pathogenesis of RA. Methods. The phenotype of CD3+, CD57+ lymphocytes was analyzed by flow cytometry, and correlations between the percentage of these cells in the blood and various clinical and biologic parameters were investigated. Results. The percentage of CD3+, CD57+ lymphocytes was increased in RA patients compared with controls. These lymphocytes expressed T cell receptor α/β. Eighty percent expressed the CD8 accessory molecule, and 20% expressed the CD4 accessory molecule. The leukocyte common antigen CD45RA isoform was expressed by these CD3+, CD57+ lymphocytes in blood. The HLA–DR antigen was expressed in synovial fluid but not in blood. Finally, the percentage of these lymphocytes in the blood correlated with the duration of RA. Conclusion. The expansion of the CD3+, CD57+ lymphocyte population and their activation in the synovial fluid of RA patients suggest that these cells are involved in the inflammatory process.     

Cd28 expression on t cell subsets in vivo and cd28-mediated t cell response in vitro in patients with rheumatoid arthritis

Objective. In view of the critical importance of the CD28–CD80 (B7/BB1) costimulatory pathway in antigen-specific T cell activation and clonal expansion, we examined CD28 surface molecule expression in vivo, and T cell receptor/CD3-mediated and B7/BB1-costimulated T cell proliferation in vitro, in rheumatoid arthritis (RA). Methods. Two-color immunofluorescence analyses of peripheral blood and synovial fluid–derived T cells, as well as ³H-thymidine incorporation assays, were performed. Results. In the peripheral blood of 31 patients with active, untreated RA, a mean of 91% (range 48–100%) of CD4+ and 46% (range 13–82%) of CD8+ T cell subsets were CD28+, which was not significantly lower than normal. Although an overall decrease in the number of T cells was not observed, the numbers of CD28+CD8+ T cells were significantly lower in RA patients (mean 233/μl, versus 292/μl in controls), and this decrease was more pronounced in patients with severe disease (mean 172/μl). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activation as assessed by HLA–DR antigen expression. In contrast to the peripheral blood, RA synovial fluid T cells were almost exclusively CD28+, suggesting that migration of CD28+CD8+ T cells to active sites of inflammation may occur. In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti-CD3 monoclonal antibody were identical in patients with RA and healthy individuals. Conclusion. Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.     

Evidence of a local intestinal immunomodulatory effect of sulfasalazine in rheumatoid arthritis

Objective. To analyze whether the intestinal mucosa in rheumatoid arthritis (RA) is immnunologically abnormal and whether sulfasalazine (SSZ) possesses any local intestinal immunoregulatory effect. Methods. Lymphocyte subpopulations and HLA—DR expression were evaluated in biopsy specimens from the duodenal—jejunal mucosa and in peripheral blood samples obtained from 17 patients with RA, both before and after 16 weeks of SSZ treatment. The same mucosal assays were also performed in 7 controls. Results. The mucosa of the small intestine in RA patients showed no differences in morphology, HLA—DR expression, or the amounts and distribution of CD3+, CD4+, CD8+, and γ/δ+ lymphocytes compared with the control group. However, there was a reduction in mucosal CD3+ and γ/δ+ lymphocyte numbers after SSZ therapy, which did not correspond to a change in peripheral blood CD3+ lymphocyte number. SSZ treatment also tended to diminish the peripheral blood CD4+:CD8+ cell ratio (P = 0.05). Conclusion. No signs of inflammation or immunologic abnormalities were seen in RA duodenal-jejunal mucosa. In this part of the intestine, however, SSZ exerted immunoregulatory effects that were not encountered in the peripheral blood.     

Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis

OBJECTIVE: We previously demonstrated that CD4+,CD25+ regulatory T (Treg) cells are present in increased numbers in the synovial fluid (SF) of rheumatoid arthritis (RA) patients and display enhanced suppressive activity as compared with their peripheral blood (PB) counterparts. Despite the presence of these immunoregulatory cells in RA, chronic inflammation persists. The purpose of the present study was to investigate whether particular proinflammatory mediators that are associated with RA could abrogate CD4+,CD25+ Treg-mediated suppression. METHODS: Monocyte phenotype was determined by flow cytometry and cytokine levels by enzyme-linked immunosorbent assay. Magnetically sorted CD4+,CD25- and CD4+,CD25+ T cells derived from the PB and SF obtained from RA patients were stimulated alone or in coculture with anti-CD3 monoclonal antibody (mAb) and autologous antigen-presenting cells, in the absence or presence of anti-CD28 mAb or the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or IL-7. RESULTS: Monocytes from the SF of RA patients displayed increased expression of HLA class II molecules, CD80, CD86, and CD40 as compared with PB-derived monocytes, indicating their activated status. Mimicking this increased costimulatory potential, addition of anti-CD28 mAb to cocultures of CD4+,CD25- and CD4+,CD25+ T cells resulted in reduced CD4+,CD25+ Treg-mediated suppression in both PB and SF. Furthermore, IL-7 and, to a limited extent, TNFalpha, both of which are produced by activated monocytes and were detected in SF, abrogated the CD4+,CD25+ Treg-mediated suppression. In contrast, IL-6 did not influence Treg-mediated suppression. CONCLUSION: Our findings suggest that the interaction of CD4+,CD25+ Treg cells with activated monocytes in the joint might lead to diminished suppressive activity of CD4+,CD25+ Treg cells in vivo, thus contributing to the chronic inflammation in RA.     

Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid arthritis patients

Objective. To examine the capacity of bone marrow progenitor cells to generate CD14+ cells, in order to assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA). Methods. CD14- cells purified from bone marrow specimens of 11 patients with active RA and 8 control patients (osteoarthritis or trauma) were cultured in the presence or absence of granulocyte–macrophage colony-stimulating factor (GM-CSF; 100 pg/ml). After incubation for various lengths of time, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. Results. The spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells was accelerated in RA patients compared with control patients. Moreover, the expression of HLA–DR on the bone marrow–derived CD14+ cells was also accelerated in RA patients compared with controls. GM-CSF significantly enhanced the generation of CD14+ cells, as well as the expression of HLA–DR, on CD14+ cells of control patients, but not those of RA patients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RA patients and control patients (undetectable in most cases). Conclusion. These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into HLA–DR+ cells play an important role in the pathogenesis of RA. Moreover, the data suggest a functional alteration of RA bone marrow CD14- cells in their responsiveness to GM-CSF.     

The immunoregulation of rheumatoid factor by the CD8 T lymphocyte subset in rheumatoid arthritis.

Flow cytometric analysis on 81 peripheral blood samples from patients with rheumatoid arthritis (RA) showed that levels of serum IgM rheumatoid factor (RF) were associated with the CD8+ cell level. A significant elevation of natural killer (CD56) cell levels was also observed in RA peripheral blood. Using in vitro antibody production techniques, CD8+ cells from patients with RA appeared to act as suppressors of RF production. Paired blood and synovial fluid samples from 9 patients with RA indicated a significant increase in SF CD8+ cells and DR+ T cells over the corresponding peripheral blood levels. The data suggest that CD8+ cells in RA may respond to immunological abnormalities occurring during the course of the disease.     

The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium

Objective. Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites. Methods. The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed. Results. Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29^bright, CD11a^bright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA—DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2–3-fold increase in migratory capacity over normal and RA PBTL. Conclusion. These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29^bright, CD11a^bright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin—. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.     

Low density of CD1+ cells in the synovial tissue of patients with rheumatoid arthritis

OBJECTIVE: CD1 molecules present microbial and self glycolipid antigens to a defined T cell subset with features of natural killer cells. CD1 molecules are up-regulated by inflammatory stimuli such as GM-CSF, and we would expect to find increased CD1 expression in the synovium of patients with rheumatoid arthritis (RA) as compared to osteoarthritis (OA). This study was initiated to compare the density of CD1a+, CD1b+, and CD1c+ synovial cells in RA and OA patients. METHODS: Expression of CD1a+, CD1b+, and CD1c+ molecules in synovial tissue was assessed by semiquantitative immunohistochemistry. For comparison, serological, functional, and typical immunohistochemical markers of inflammation were detected. RESULTS: Although patients with RA as compared to OA had highly significantly increased signs of inflammation, the density of CD1a+, CD1b+, and CD1c+ synovial cells was similar This was also true for the density of CD1+ cells in relation to that of activated CD163+ macrophages. There was a high correlation between the densities of CD1a,b,c positive cells, which suggests the existence of similar regulatory pathways. In a combined analysis of RA and OA patients, there existed a negative association between prior NSAID therapy and the density of CD1a+, CD1b+, and CD1c+ synoviocytes in relation to CD163+ macrophages. This is interesting because a similar immunosuppressive aspect of NSAID has never been shown before and this might represent a hitherto unrecognized immunosuppressive aspect of NSAID. CONCLUSION: Considering the high synovial inflammation in patients with RA, the densities of CD1a+, CD1b+, and CD1c+ synovial cells were low compared to patients with OA. Further studies in RA patients are needed to clarify whether a defect in CD1 regulation may exist. Such a defect may lead to an insufficient immune response against microbial glycolipids, which would support smoldering or repeated inadequately responded infection.