CD40-CD40L在强直性脊柱炎患者外周血淋巴细胞上的表达

目的探讨共刺激分子CD40CD40L在强直性脊柱炎(AS)患者的外周血淋巴细胞亚群上的异常表达与免疫功能紊乱的关系。方法用流式细胞仪采用直接免疫荧光法测定30例AS患者和20例健康对照人外周血淋巴细胞表面标志CD3、CD4、CD8、CD19的表达情况,CD40L在CD4 T和CD8 T细胞上的表达及CD40在CD19 B细胞上的表达。用速率散射比浊法测定血清中免疫球蛋白IgG,IgA和IgM的水平。结果①AS患者CD3 、CD3 CD4 、CD19 细胞较正常对照组显著增高(P<0.05),CD3 CD8 细胞较正常对照组显著降低(P<0.05);②AS患者CD4 T细胞和CD8 T细胞上的CD40L、CD19 B细胞上CD40的表达都较对照组显著增高(P<0.05);③AS患者血清中2种免疫球蛋白IgG、IgA的水平均较对照组显著增高(P<0.05)。结论CD40CD40L途径在AS免疫功能紊乱中起了重要作用。     

重症肌无力患者CD4、CD8细胞表面Fas分子的变化

为探讨Fas分子、CD4、CD8分子在重症肌无力发生中的作用 ,从胸腺及外周血分离单个核细胞 ,用荧光标记的单克隆抗体 (Fas FITC、CD4 PE、CD8 Cy )和流式细胞仪检测细胞表面Fas、CD4、CD8表达情况。结果发现 ,(1)MG患者外周血单个核细胞 (PBMC )CD4 + CD8 细胞明显低于对照组 (P <0 0 2 ) ;(2 )MG患者Fas分子在PBMC的表达率明显低于对照组 (P<0 0 2 ) ,Fas+ CD4 + 细胞也低于对照组 (P <0 0 5 ) ;(3)在Fas+ 的胸腺细胞中 ,MG患者的双阳性细胞显著低于对照组 (P <0 0 1) ,而CD4 CD8+ 细胞则高于对照组 (P <0 0 5 )。说明重症肌无力患者淋巴细胞存在Fas表达异常 ,表现为外周CD4 + 细胞活化后的凋亡障碍和胸腺CD4 + CD8+ 细胞凋亡障碍 ,可能与重症肌无力患者自身反应性T细胞的形成及疾病的发生有关     

慢性肾炎患者外周血T细胞亚群和共刺激分子的表达及其意义

为研究慢性肾炎患者外周血T细胞亚群和共刺激分子的表达特点及其在慢性肾炎免疫病理机制中的作用 ,本文采用免疫荧光标记和流式细胞仪分析 ,对 35例慢性肾炎患者外周血T淋巴细胞亚群和共刺激分子CD2 8、 4 1BB等的表达进行研究。结果表明 :(1)慢性肾炎患者T细胞亚群明显失衡 ,表现为CD4减少 ,CD8增加 ,CD4/CD8比值显著降低 ;(2 )共刺激分子CD2 8表达显著低于正常对照组 (CD2 8表达百分率分别为 45 95± 5 6 7和 6 6 42± 4 5 8,P <0 0 0 1) ,且CD4+ CD2 8+ T细胞和CD8+ CD2 8+ T细胞均显著减少。治疗后缓解期患者T细胞亚群失衡明显纠正 ,CD2 8+ T细胞 ,尤其是CD4+ CD2 8+ T细胞显著增多 ,而且CD4+ CD2 8+ T细胞数与患者的 2 4h尿蛋白定量呈负相关 (r= 0 47,P <0 0 1) ;(3)慢性肾炎患者共刺激分子 4 1BB在T细胞中的表达显著高于正常对照组 (表达百分率分别为 30 5 7± 8 12和 0 74± 0 2 8,P <0 0 0 1) ,治疗后的 4 1BB表达水平显著降低 ,而且 4 1BB异常高表达与CD8+ T细胞数呈正相关 (r=0 6 3,P <0 0 5 )。从而表明慢性肾炎外周血T细胞亚群失衡和T细胞活化所必需的共刺激分子CD2 8、 4 1BB异常表达 ,可能在慢性肾炎发生和病变进展中起着重要作用。     

重症肌无力患者外周血CD5~+B细胞和CD4~-CD8~-T细胞的变化

研究重症肌无力 (MG )患者外周血CD5 + B细胞和CD4 CD8 T细胞的变化 ,以探讨这两种细胞与MG的关系。采用流式细胞仪分析MG患者和对照组外周血中CD5 + B细胞和CD4 CD8 T细胞的频率 ,同时以ELISA方法检测这些患者的血清AchR、PsmR抗体水平。结果 :2 8例MG患者的CD5 + B细胞为 19 75 %± 10 8% ,高于对照组的 15 4 %± 9 6 7% (P <0 0 1) ;胸腺未切除MG患者的CD5 + B细胞为 2 2 31%± 7 4 7% ,显著高于对照组 (P <0 0 0 1) ;两种抗体阳性MG患者的CD5 + B细胞为 2 4 96 %± 13 1% ,显著高于对照组 (P <0 0 0 1) ;以上各组MG患者的CD4 CD8 T细胞与对照组均无显著区别 ;两种抗体阴性组的CD5 + B细胞和CD4 CD8 T细胞亦与对照组均无显著区别 ;两种抗体阴性组的CD5 + B细胞和CD4 CD8 T细胞亦与对照组无明显差异。本研究提示MG患者外周血的CD5 + B细胞频率增高 ,与胸腺切除与否以及突触前后膜抗体的阳性程度密切相关 ,而CD4 CD8 T细胞是否与MG有关还需进一步研究证实。     

淋巴细胞共刺激信号和凋亡信号异常与RA免疫效应亢进的研究

目的：探究T淋巴细胞表面多种细胞信号分子所介导的细胞活化或凋亡信号在RA患者免疫功能紊乱中的作用。方法：采用流式细胞术检测RA患者外周血T细胞亚群及其表面共刺激分子cD154（cD40L）、CD30和凋亡受体CD95（Fas）的表达。结果：RA患者外周血T细胞亚群偏移，CD4^＋T细胞增加，CD8^＋T细胞减少；共刺激分子CD154在CD4^＋和CD8^＋T细胞上的表达均上调，但CD30分子的表达均降低，并以CD4^＋T细胞降低更为明显。同时，凋亡受体CD95分子在T细胞亚群上的表达均明显增加。结论：RA患者T淋巴细胞表面多种信号分子表达异常，共同导致了RA患者免疫功能紊乱。     

Graves病患者外周血T细胞亚群和共刺激分子的表达及其意义

为研究Graves病患者外周血T细胞亚群及共刺激分子的表达 ,并探讨其在Graves免疫病理机制中的作用 ,本文采用免疫荧光标记和流式细胞仪术检测了 19例Graves病患者和 11例正常人外周血T细胞亚群及共刺激分子 (CD2 8、B7、CD40、CD40L、 4 1BB、OX40 )的表达。结果表明 ,19例初诊Graves病患者外周血T细胞亚群呈现异常改变 ,表现为CD3+ 和CD4+T细胞显著下降 (P <0 0 5 ,P <0 0 1) ,CD4+ /CD8+ T细胞比值倒置 (P <0 0 1) ,共刺激分子CD2 8在T细胞中的表达水平明显下降 (P <0 0 1) ,T细胞亚群CD4+ CD2 8+ 、CD8+ CD2 8+ 细胞数量均减少 (P <0 0 5 ,P <0 0 1) ,而 4 1BB分子表达显著地升高 (P <0 0 5 )。随防 10例治疗后缓解患者 ,T细胞亚群失衡明显改善 ,共刺激分子CD2 8的表达水平上调 (P <0 0 1) ,而4 1BB分子的表达明显下降 (P <0 0 1) ,T细胞亚群CD4+ CD2 8+ 、CD8+ CD2 8+ 细胞数量均增加 (P <0 0 1) ,甲状腺自身抗体甲状腺球蛋白抗体 (TGAb )和甲状腺微粒体抗体 (TMAb )的表达水平均下降 (P <0 0 1,P <0 0 1)。从而表明 ,T细胞亚群的异常及共刺激分子CD2 8、 4 1BB的表达改变与Graves病的免疫病理机制相关。     

尖锐湿疣患者外周血T淋巴细胞上活化抗原的表达

目的 :探讨尖锐湿疣 (CA)患者外周血CD6 9和HLA DR分子在T淋巴细胞上表达的变化及其意义。方法 :采用免疫荧光三标记流式细胞术检测 30例CA患者外周血T细胞CD6 9和HLA DR抗原的表达 ,并以 31例正常人作为对照。结果 :CA患者外周血CD3 T细胞CD6 9的表达 (6 6 3%± 3 13% )与正常人对照组 (5 12 %± 1 6 4 % )相比 ,差异有显著性 (P <0 0 5 ) ,CD4 T细胞CD6 9的表达与正常人对照组相比 ,差异无显著性 (P >0 0 5 ) ,CD8 T细胞表达CD6 9水平 (4 6 1%± 3 0 9% )明显高于对照组 (2 6 7%± 1 31% ,P <0 0 1) ;患者组CD3 T细胞中HLA DR 细胞 (2 1 6 5 %± 8 84 % )比对照组 (13 5 6 %± 5 15 % )显著增高 (P <0 0 0 1)。结论 :CA患者外周血T淋巴细胞的激活以CD8 T细胞为主 ,其免疫激活状态在抗病毒感染中起着重要作用。     

共刺激信号分子表达异常与自身免疫性疾病的关系

目的 分析类风湿性关节炎（RA）和系统性红斑狼疮（SLE）细胞免疫异常中共刺激活化信号途径的异同点,探讨细胞活化的共刺激信号途径对于RA和SLE发病的意义。方法 采用流式细胞术分析SLE和RA患者T细胞表面共刺激分子CD28、CD152／CTLA-4、CD154／CD40L和ICOS表达情况。结果 ①RA患者CD4^＋T细胞比例明显增加,SLE患者以CD8^＋T细胞增加显著。②SLE患者CD4^＋和CD8^＋T细胞上CD28和CD152的表达增加;RA患者T细胞亚群上CD28分子的表达减少,CD152分子的表达增加。③RA患者CD4^＋T细胞上CD154分子表达增加,CD8^＋T细胞上CD154分子表达减少,T细胞亚群上可诱导共刺激分子（ICOS）的表达无明显变化;SLE患者CD4^＋和CD8^＋T细胞上CD1254或ICOS分子的表达均减少。结论 RA和SLE患者机体的免疫异常中存在着明显的分子信号途径差异。     

骨髓增生异常综合征患者先天性免疫细胞数量和功能分析

目的:检测骨髓增生异常综合征(Myelodysplatic syndrome,MDS)患者先天性免疫细胞数量并分析其功能变化.方法:采用流式细胞仪检测了97例MDS病人的免疫功能.健康对照34名.结果:Refractory Anemia (RA)和Refractory Anemia with Excess Blasts (RAEB)患者的CD3- (CD16 CD56)+(NK)细胞百分率与正常对照组无明显差异.RAEB患者的CD56+细胞中颗粒酶和穿孔素的百分率均较正常对照组明显升高(P＜0.05),而RA患者与正常对照组相比无明显差异.RA和RAEB患者的CD3+CD56+细胞百分率均显著高于正常对照组(P＜0.001);Vα24+CD161+NKT细胞在RA患者中的表达明显增加(P＜0.05),RAEB患者无明显变化(P＞0.05);Vα 24+CD161-细胞在RA患者CD4+、CD8+细胞中的表达明显减少(P＜0.05);而CD4-CD8- NKT细胞与对照组比无明显差异;RAEB患者Vα24+细胞的表达与正常对照组无明显差异.γδT细胞在RAEB患者CD4-CD8-细胞中的表达较正常对照组明显减少(P＜0.05).结论:MDS患者可能存在明显的免疫功能紊乱.     

重症肌无力患者外周血中CD4~+CD25~+调节性T细胞的变化及意义

研究CD4 + CD2 5 + 调节性T细胞在重症肌无力 (MG )发病中的作用。本文采用三色流式细胞术对 2 9例MG患者和 2 3例健康对照者外周血中CD4 + CD2 5 + T细胞 (CD3+ CD4 + CD2 5 + )的百分率进行测定。结果显示病情未能很好控制的MG患者外周血CD4 + CD2 5 + T细胞比率略低于健康对照组 (分别为 3 79%± 1 4 0 %、 4 5 3%± 0 96 % ,P =0 12 ) ,病情稳定或缓解的MG患者CD4 + CD2 5 + T细胞比率 (8 4 5 %± 1 96 % )显著高于健康对照组 (P =0 0 0 0 1) ;胸腺切除的MG患者CD4 + CD2 5 + T细胞比率 (8 4 4 %± 2 39% )显著高于非胸腺切除的MG患者 (5 88%± 2 89% ,P =0 0 38)和健康对照组 (4 5 3%± 0 96 % ,P =0 0 0 3)。提示MG患者外周血中存在异常比例的CD4 + CD2 5 + 调节性T细胞 ,可能参与疾病的发生与发展。     

Aberrant T-regulation in rheumatoid arthritis and IgA nephropathy affects CD5+ and CD5- B lymphocytes equally.

T-suppressor function and T-helper function in healthy adults, elderly patients with non-immune diseases, and patients with rheumatoid arthritis (RA) and IgA nephropathy (IgAN) were titrated by adding graded concentrations of CD8+ cells to autologous CD8-depleted peripheral blood mononuclear cells (PBMC), or CD4+ cells to CD8- 4- PBMC, respectively. Following culture with pokeweed mitogen (PWM), numbers of CD5+ and CD5- immunoglobulin-secreting cells were determined using a combination of rosetting with anti-CD5-coated Dynabeads and reverse haemolytic plaque formation (Jones, 1990). Of 11 RA patients studied, eight had slightly reduced suppressor activity for CD5+ and CD5- IgM-secreting cells, and three with active disease and high serum levels of C-reactive protein, could not suppress IgG, IgA or IgM secretion by either B subset. Helper activity for both CD5+ and CD5- B cells was slightly but significantly increased in RA patients. One of eight patients with IgAN could not suppress IgG, IgA or IgM production by CD5+ or CD5- B cells, and all IgAN patients required strikingly fewer CD4+ cells for PWM-induced activation of CD5+ and CD5- B cells than controls. It was concluded that in two immunologically mediated diseases in which some patients have raised numbers of circulating CD5+ B cells, aberrant T-regulation affects CD5+ and conventional CD5- B cells equally.     

Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells

Chronic lymphocytic leukemia (CLL) is associated with impaired immunoglobulin (Ig) class-switching from IgM to IgG and IgA, a defect that leads to recurrent infections. When activated in the presence of leukemic CLL B cells, T cells rapidly up-regulate CD30 through an OX40 ligand and interleukin 4 (IL-4)-dependent mechanism. These leukemia-induced CD30+ T cells inhibit CD40 ligand (CD40L)-mediated S mu-->S gamma and S mu-->S alpha class-switch DNA recombination (CSR) by engaging CD30 ligand (CD30L), a molecule that interferes with the assembly of the CD40-tumor necrosis factor receptor-associated factor (TRAF) complex in nonmalignant IgD+ B cells. In addition, engagement of T cell CD30 by CD30L on neoplastic CLL B cells down-regulates the CD3-induced expression of CD40L. These findings indicate that, in CLL, abnormal CD30-CD30L interaction impairs IgG and IgA production by interfering with the CD40-mediated differentiation of nonmalignant B cells.     

Expression of CD40 and CD40 ligand among cell populations within rheumatoid synovial compartment

Augmented and prolonged expression of CD40 ligand (CD40L) was recently reported in lymphoid cells from human lupus patients, suggesting that CD40/CD40L pathway was involved in the pathogenesis of systemic autoimmune diseases. This study was thus designed to study the expression of CD40 and CD40L among cell populations within inflammatory joints of patients with rheumatoid arthritis (RA). The result showed that most B cells and monocytes in synovial fluids (SF) expressed CD40. Cultured synovial fibroblasts also stained positive for CD40. Regarding CD40L, we found that T cells as well as B cells could express CD40L. Compared with normal controls, RA patients had higher levels of CD40L+ T cells (8.71 +/- 17.69% vs 1.74 +/- 2.30%, P > 0.05) and CD40L+ B cells (7.71 +/- 7.64% vs 1.12 +/- 1.59% P < 0.05). After in vitro stimulation, T cells from RA patients had higher and longer CD40L expression than T cells from normal peripheral blood. For investigating the effect of CD40 expressed on synovial fibroblasts on TNF-alpha production in joint compartment, we used anti-CD40 antibody to bind CD40 on fibroblasts for one hour and then co-cultured with synovial fluid mononuclear cells. We found that the levels of TNF-alpha decreased in the presence of anti-CD40 antibody. We concluded that there was an intrinsic hyperexpression of CD40L on lymphoid cells within rheumatoid joints, and synovial fibroblasts could contribute to articular inflammation through surface CD40 molecule.     

Children with chronic renal failure have reduced numbers of memory B cells

Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failure, with or without dialysis treatment. B cell subsets were characterized by determining CD27, IgM, IgD and CD5 expression within the CD19(+) population. Intracellular expression of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 in PMA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) was used to evaluate T helper frequencies. The capacity of B cells to secrete Ig in vitro was determined by measuring IgG(1), IgG(2) and IgM in culture supernatants of anti-CD2/CD28 monoclonal antibody (MoAb)- or SAC/IL-2-stimulated PBMC. Memory B cell numbers (identified as percentage or absolute number of CD19(+) IgM-IgD- or CD19(+)CD27(+) lymphocytes) were lower in children treated with haemodialysis (HD), peritoneal dialysis (PD) and children with chronic renal failure before starting dialysis treatment (CRF) compared to healthy controls (HC) (P < 0.05). Compared with HC, CD5(+) (naive) B cells were reduced in HD-treated patients but not for PD or for children with chronic renal failure before starting dialysis treatment (CRF). No significant differences in CD4(+) T helper cell subsets were found between the groups. However, CRF children had a higher percentage of IFN-gamma producing CD8(+) T lymphocytes compared to HC (P = 0.02). Finally, IgG(1), IgG(2) and IgM production in vitro was similar in the four groups. In conclusion, significantly lower numbers of memory type B cells were found in children with chronic renal failure compared to healthy controls. This reduction may contribute to the low Ig levels found in these children.     

Differential requirements for induction of total immunoglobulin and physiological rheumatoid factor production by human peripheral blood B cells

Rheumatoid factors (RFs) are autoantibodies directed against the Fc part of IgG. Considerable evidence exists that there are two classes of RFs, pathological and physiological. Whereas pathological RFs are associated with disease, physiological RFs are considered to be a normal component of the immune response. RF(+) precursor B cells present as part of the B cell repertoire of healthy individuals are held responsible for the production of physiological RFs, which is a transient phenomenon with a clear correlation with an initiating stimulus such as immunization or exposure to an infection. Here we demonstrate a difference in the regulatory control of total Ig and RF production by peripheral blood (PB) B cells of both healthy controls (HC) and patients with rheumatoid arthritis (RA). Highly purified B cells from HC and patients with RA were cocultured with T cells stimulated with immobilized anti-CD3 mAb. Similar to IgM production, IgM-RF production was shown to be dependent on CD40 cross-linking. However, activation of PB B cells in the CD40 system in the presence of IL-2, IL-4, IL-10, combinations of these cytokines or supernatant of anti-CD3-stimulated T cells failed to induce detectable IgM-RF, whereas total IgM production was considerable. From these results we conclude that conditions to activate physiological RF(+) B cells require additional contact besides CD40--CD40L interactions between T and B cells. Since the requirements for RF production were similar using PB B cells from HC and patients with RA it is suggested that the regulatory properties of RF(+) precursors in the PB B cell compartment is equal among these groups. Together, these results indicate that conditions for the induction of total Ig and physiological RFs are different.     

Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients

Common variable immunodeficiency (CVID) is primary hypogammaglobulinaemia with an unknown aetiopathogenesis. Although various abnormalities of T and B cells have been described, their pathogenetic roles are unclear. We determined T and B lymphocyte subsets known to be abnormal in CVID in order to disclose possible relations between numerical abnormalities in those cells. Markers associated with B cell development (CD21, CD27, IgM, IgD) were determined on B lymphocytes (CD19+); T lymphocyte development (CD45RA, CD45RO, CD62L) and activation markers (CD25, CD27, CD28, CD29, CD38, CD57, HLA-DR) were determined on CD4+ and CD8+ T lymphocytes in 42 CVID patients and in 33 healthy controls. Abnormalities in CD4+ T lymphocyte activation markers (increase in CD29, HLA-DR, CD45RO, decrease in CD27, CD62L, CD45RA) were observed particularly in patients with a decreased number of memory (CD27+) and mature (CD21+) B cells (group Ia according to the Freiburg group's classification), while abnormalities observed in CD8+ cells (increase in CD27 and CD28 and decrease in HLA-DR, CD57 and CD38) did not depend upon grouping patients together according to B lymphocyte developmental subpopulations. We observed correlations between immature B cells (IgM+ CD21-) and expression of CD27, CD62L, CD45RA, CD45RO and HLA-DR on CD4+ T cells in CVID patients but not in the control group. The expression of CD27 and CD45RA on CD4+ T lymphocytes, such as the percentage of IgD+ CD27- and IgD+ CD27+ cells in B lymphocytes, showed age dependency to be more significant than in the control group. Our study demonstrates that T and B lymphocyte abnormalities in CVID are partially related to each other. Some of those abnormalities are not definite, but may evolve with age of the patient.     

T-Cell Helper Activity and B-Cell Function of Synovial and Blood Lymphocytes from Patients with Rheumatoid Arthritis or Other Forms of Chronic Arthritis

The helper effect of T cells on B-cell immunoglobulin (Ig) responses induced by pokeweed mitogen (PWM) or purified protein derivative of tuberculin (PPD) was studied in lymphocytes from synovial fluid (SF) and blood of nine patients with rheumatoid arthritis (RA) and eight patients with other forms of chronic arthritis. In PWM cultures the helper effect of SF T cells on Ig responses (IgG, IgM, IgA) of autologous and allogeneic blood B cells was lower than that of blood T cells (P less than 0.01). This decrease was more pronounced in patients with RA than in patients with non-RA. In PPD cultures no significant difference was found between the helper effect of SF T cells and blood T cells on the Ig responses of allogeneic blood B cells or on the IgG response of autologous blood B cells, whereas the helper effect of SF T cells on the IgM and IgA responses of autologous blood B cells was decreased. The Ig responses to PWM or PPD in cocultures of autologous blood B and T cells were not significantly different between patients and healthy controls. The PWM- and PPD-induced Ig responses of SF B cells were lower than those of blood B cells when cocultured with autologous blood T cells. SF B cells produced IgG but usually little IgM and IgA. Thus there was a dysfunction of SF B cells and of SF T cells in a PWM-driven system, but a fairly good helper function of SF T cells in a PPD-driven system.     

Impaired up-regulation of CD70 and CD86 in naive (CD27-) B cells from patients with common variable immunodeficiency (CVID)

CVID is characterized by reduced serum levels of all switched immunoglobulin isotypes (IgG, IgA, IgE) predisposing patients to recurrent infections of their respiratory and gastrointestinal tract. Correspondingly, most CVID patients exhibit a severely decreased proportion of class switched memory B cells (CD19+CD27+IgD-IgM-IgG+ or IgA+) in their peripheral blood (CVID type I). We previously identified a subgroup of CVID patients showing a significantly reduced expression of CD86 and CD137 following activation in vitro of PBMC or purified B cells (CD19+) with anti-IgM plus IL-2. Here we extend our previous studies by asking whether highly purified, cell-sorted naive B cells show already an expression defect of B cell surface molecules relevant in activation (CD39, CD69), differentiation (CD24, CD27, CD38) or T-B interaction (CD25, CD70, CD86). We stimulated cell-sorted, naive B cells (CD19+CD27-IgM+IgDhighIgG-IgA-) from 10 CVID patients and 10 healthy controls for 4 days with anti-IgM plus IL-2 in the absence or presence of autologous CD4+ T cells and measured the expression of the referred surface molecules. Based on reduced or normal numbers of switched memory B cells the CVID patients had previously been classified into eight type I patients and two type II patients, respectively. Interestingly, only the molecules CD25, CD70 and CD86, all relevant in cognate T-B interaction, showed a significantly lower expression in naive B cells from CVID patients compared to controls. While coculture with autologous CD4+ T cells normalized the CD25 expression, CD70 and CD86 expression remained subnormal, notably in the eight CVID patients of type I. These findings strongly suggest an intrinsic signalling or expression defect for CD70/CD86 at the level of naive B cells in type I CVID patients.