胰腺癌趋化因子表达与肥大细胞计数的相关性

目的　探讨胰腺癌组织中肥大细胞计数(MCC)和IL- 8、MCP- 1、MIP-1α表达及其相互关系。方法　对51例胰腺癌组织进行肥大细胞计数,并采用免疫组化染色(ABC法)观察趋化因子的表达情况。结果　胰腺癌MCC均值为(16 1±6 8)个/HP;IL- 8、MCP- 1和MIP -1α表达阳性率分别为62 7%、66. 7%和66. 7%,评分均值为2. 9±1. 9、2. 6±1 .8和2 4±1 7。高分化腺癌和未转移癌MCC明显低于低分化腺癌和转移癌(P<0 .05,P<0 .01 )。高分化腺癌IL -8评分明显低于低分化腺癌(P<0. 05);未转移病例IL- 8、MCP- 1、MIP- 1α表达阳性率及评分明显低于转移癌(P<0 .05,P<0. 01)。IL-8、MCP- 1和MIP- 1α阳性病例MCC明显低于阴性病例(P<0. 01)。MCC与IL-8(r=0 47)、MCP- 1(r=0 .56)和MIP- 1α(r=0 .39)评分值之间均呈密切正相关,IL 8与MCP 1(r=0 .54)、MIP -1α(r=0. 52)及MCP- 1与MIP- 1α(r=0. 61)之间均呈密切正相关。结论　MCC和IL -8、MCP -1、MIP- 1α表达可能是反映胰腺癌进展、转移发生和预后的重要标记物, 3种趋化因子可能具有促进MC肿瘤内浸润的作用或MC促进癌细胞3种趋化因子的表达。     

雷藤舒(LLDT-8)对成纤维样滑膜细胞分泌趋化因子的影响

研究(5R)-5-羟基雷公藤内酯醇(雷藤舒,LLDT-8)对TNF-α联合IL-17诱导类风湿关节炎(rheumatoid arthritis,RA)成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)分泌趋化因子GRO-α、ENA-78、MCP-1、MIP-1α和RANTES的影响。ELISA法检测FLS上清液中GRO-α、ENA-78、MCP-1、MIP-1α和RANTES的浓度;RT-PCR法检测FLS中GRO-α、ENA-78、MCP-1、MIP-1α和RANTES mRNA的表达。结果显示LLDT-8可显著抑制TNF-α联合IL-17诱导的FLS上清液中GRO-α、ENA-78、MCP-1、MIP-1α和RANTES的表达;也可有效抑制TNF-α联合IL-17诱导的FLS GRO-α、ENA-78、MCP-1、MIP-1α和RANTES mRNA的表达。该研究提示LLDT-8通过抑制FLS产生GRO-α、ENA-78、MCP-1、MIP-1α和RANTES而在RA的治疗中发挥抗炎作用。     

IL-38通过上调CXCL1及IL-8募集中性粒细胞促进转移病灶的形成研究

目的:探讨IL-38在肿瘤患者肿瘤组织中的表达水平及其对肿瘤转移病灶形成的影响。方法:本研究共纳入2009年1月~2014年12月我院收治的32例转移性肿瘤患者和62例原位癌患者作为研究对象。另选取43例同期在我院体检中心进行体检的健康人员作为对照。采用ELISA法(酶联免疫吸附法)检测各组研究对象血清IL-38水平。免疫组化分析转移性肿瘤患者及原位癌患者组织IL-38、CXCL1及IL-8的表达。建立小鼠肺转移模型,分别用B16F1与B16F0细胞尾静脉注射C57小鼠,然后小鼠肝脏转染IL-38,间隔48 h重复转染。两周后统计分析小鼠肺组织转移病灶数。免疫组化检测小鼠肺组织中性粒细胞浸润、CXCL1及IL-8水平。Realtime-PCR检测肺组织中趋化因子CXCL1与IL-8的表达。肺转移模型小鼠转染IL-38后,给予小鼠CXCL1及IL-8抑制剂。比较各组小鼠肺组织转移病灶数及中性粒细胞浸润情况。Western blot检测各组小鼠肺组织中IL-38、CXCL1、IL-8的表达及MEK、ERK的磷酸化水平。结果:肺转移肿瘤患者的血清IL-38水平显著高于原位癌及健康者(P0.05),其肿瘤组织中IL-38、CXCL1及IL-8的表达水平均显著高于原位癌患者(P0.05)。IL-38能显著增加B16F1在C57小鼠肺部形成转移病灶的数量(P0.05),且能促进不易发生转移的B16F0在肺部形成明显的转移病灶。组化结果显示,IL-38能显著增加小鼠肺组织中性粒细胞的浸润(P0.05)。Realtime-PCR结果显示,IL-38转染能显著增加肺组织中CXCL1及IL-8的表达(P0.05)。给予CXCL1及IL-8抑制剂能显著抑制IL-38引起的小鼠肺部病灶数增加及肺组织中性粒细胞浸润(P0.05)。Western blot结果显示,IL-38转染能显著上调肺转移小鼠模型肺组织中CXCL1、IL-8的表达及MEK、ERK的磷酸化水平,给予CXCL1及IL-8抑制剂能显著抑制IL-38对MEK、ERK磷酸化的影响。结论:肺转移肿瘤患者的血清和肿瘤组织中IL-38水平均显著升高,IL-38可能通过上调CXCL1、IL-8及MEK、ERK的磷酸化水平募集中性粒细胞,从而促进转移病灶的形成。     

环孢菌素A抑制小鼠同种心脏移植急性排斥反应中Lymphotactin表达的研究

目的：研究小鼠同种心脏移植急性排斥反应中淋巴细胞趋化因子（lptn）的表达情况及环孢菌素A（cyclosporine A, CsA）的抑制作用。 方法： 改良Banff评分系统判断同种小鼠移植心急性排斥反应程度，RT-PCR检测移植心组织内淋巴细胞趋化因子表达水平，ELISA方法检测心脏移植小鼠脾细胞活化T细胞核因子(NFAT)活性。 结果： C57BL/6-Balb/c急性排斥组小鼠移植术3 d后脾脏显著增大。术后第5、7 d移植心肌间淋巴细胞浸润程度评分分别为2.667±0.577和2.333±0.577。C57BL/6-Balb/c+CsA组小鼠移植术后脾脏肿大明显减轻，术后第5、7 d心肌间淋巴细胞浸润程度评分分别为1.000±0.000和1.333±0.577。急性排斥组和CsA处理组小鼠移植心脏在术后第5 d和第7 d都可检测到Lptn mRNA阳性表达，但CsA处理组Lptn mRNA的表达明显弱于急性排斥组。治疗剂量的CsA可以完全抑制NFATc1活性。 结论： Lptn在早期移植免疫事件中具有重要的作用，CsA仅能部分抑制Lptn mRNA的表达。活化T细胞Lptn的表达调控存在NFAT以外的途径。     

硫辛酸抑制脂多糖诱导的星形胶质细胞细胞因子及趋化因子的表达

目的探讨硫辛酸(LA)对脂多糖(LPS)激活的星形胶质细胞分泌TNF-α、IL-1β、IL-6和IL-10及相关趋化因子的影响。方法分离并鉴定新生C57BL/6小鼠大脑皮质星形胶质细胞,1μg/mL LPS刺激第2代星形胶质细胞,100μg/mL LA进行干预,Griess法检测NO的分泌,ELISA检测TNF-α、IL-1β、IL-6和IL-10炎性因子的含量,反转录PCR检测炎症趋化因子CC亚族趋化因子配体20(CCL20),单核细胞趋化蛋白1(MCP-1)和巨噬细胞炎性蛋白1α(MIP-1α)mRNA的表达。结果与正常组比较,LPS刺激星形胶质细胞后,NO、TNF-α、IL-1β、IL-6分泌显著升高,IL-10分泌下调(P0.05);LA能抑制LPS诱导的NO、TNF-α、IL-1β、IL-6的分泌,增加IL-10的分泌,与LPS组相比差异有统计学意义(P0.05)。LA能显著下调LPS所致的CCL20、MIP-1α、MCP-1 mRNA的分泌。结论 LA能抑制LPS激活星形胶质细胞所致的炎性反应,其作用与抑制炎性因子及趋化因子的分泌有关。     

CXCL8/CXCR1驱动FOXS1蛋白促进食管癌ECA109细胞增殖、侵袭及迁移

为了探讨CXC趋化因子配体8(CXC motif chemokine ligand 8,CXCL8)/CXC趋化因子受体1(CXC chemokine receptor 1,CXCR1)对体外人食管癌细胞ECA109增殖、凋亡及侵袭迁移的影响，并观察其与叉头框家族S1(forkhead box S1,FOXS1)蛋白的关系，将人食管癌细胞ECA109转染后分为对照组、CXCL8组、CXCL8+Con-siRNA组和CXCL8+CXCR1-siRNA组。CXCL8终浓度为10μg/mL。采用MTT试验检测细胞增殖情况，克隆试验检测克隆形成情况，流式细胞仪进行细胞凋亡测试，侵袭与迁移能力由Transwell试验和划痕试验测定，Western blotting检测细胞中CXCR1、FOXS1蛋白表达水平。结果显示，与对照组比较，CXCL8能够显著促进ECA109细胞增殖、克隆、侵袭和迁移(P<0.05),而干扰CXCR1后这些作用被阻断(P<0.05)。CXCL8组、CXCL8+Con-siRNA组细胞凋亡率与对照组比较，差异无统计学意义(P>0.05),CXCL8+CXC...     

星形细胞瘤和髓母细胞瘤患儿血清IL-6、IL-8和MIP-1α水平变化

目的 研究星形细胞瘤和髓母细胞瘤患儿血清IL-6、IL-8和MIP-1α含量变化及临床意义.方法 应用Luminex 200多功能液相芯片分析仪检测54例健康儿童和55例星形细胞瘤、46例髓母细胞瘤患儿血清IL-6、IL-8和MIP-1α浓度.结果 两肿瘤组血清IL-6、IL-8、MIP-1α浓度均显著高于正常对照组(均P＜0.01),而且星形细胞瘤组IL-6水平显著高于髓母细胞瘤组(P＜0.01),两组患儿血清中三种细胞因子浓度两两正相关(均P＜0.01).男、女患儿间比较,星形细胞瘤组只有IL-6水平差异具有统计学意义(P＜0.05);髓母细胞瘤组IL-6、MIP-1a水平差异均有统计学意义(均P＜0.05).结论 血清IL-6、IL-8和MIP-1α浓度变化与儿童恶性脑肿瘤的发生密切相关,三种因子彼此间协同发挥作用.     

供肝NK细胞对肝移植免疫反应中NF-κB 活性和IL-15表达的影响

 目的：观察大鼠移植肝组织内和外周血白细胞介素15（IL-15）的表达水平及脾组织内核因子κB(NF-κB)的表达活性变化,探讨供肝NK细胞减轻肝移植术后急性排斥反应的机制。方法：Lewis大鼠为肝移植供体,BN大鼠为受体,改良“二袖套”法建立大鼠肝移植模型。应用［60Co］射线照射清除供体免疫细胞和经门静脉回输供肝NK细胞等技术,实验设立3组。A组: 急性排斥组;B组: 单纯［60Co］照射排斥组;C组: ［60Co］照射+供肝NK细胞门静脉回输排斥组。移植术后第1、3、7天收集受鼠外周血清,ELISA法检测IL-15分泌水平,同时切取移植肝行病理学检查,Western blotting法检测移植肝组织IL-15蛋白的表达,凝胶电泳迁移实验（EMSA）检测受鼠脾组织NF-κB表达活性。另外每组各设亚组观察移植后大鼠自然生存时间。结果：B组术后大鼠自然存活时间较A、C组明显缩短,术后发生急性排斥反应程度较A、C组严重;术后第3、7天,3组受鼠外周血IL-15水平均较第1天时显著升高;移植术后第3、7天,B组大鼠血清IL-15 浓度均显著高于A、C组;术后第3、7天,移植肝组织中B组IL-15表达也显著高于A、C组,受鼠脾组织中B组NF-κB表达活性亦显著高于A、C组。结论：IL-15可能作为肝移植急性排斥反应的监测指标,对急性排斥反应的早期诊断和移植物的预后估计具有临床指导意义;供肝NK细胞可能通过下调NF-κB的表达活性来调节IL-15的水平,进而减轻肝移植术后急性排斥反应。     

肾移植患者肿瘤坏死因子-α动态检测的临床意义

目的 :动态观察肾移植患者肿瘤坏死因子 -α(TNF -α)水平的变化 ,探讨TNF -α对肾移植预后的意义。方法 :采用放射免疫分析检测 4 5例肾移植患者术前及术后两天血清及尿液中TNF -α的水平 ,并与 4 5例正常对照者进行对比分析。对 33例术后稳定者 ,动态检测术后 2d、7d、14d、2 1d及 2 8d血清及尿液中TNF -α的水平。结果 :术前组、术后稳定组、术后排斥组、CsA中毒组血清TNF -α水平均显著高于正常对照组 (P <0 0 1) ,术后排斥组显著高于术前组及术后其他各组 (P <0 0 1) ;术前组和术后稳定组尿液TNF -α水平均显著高于正常对照组 (P <0 0 1) ,术后排斥组尿液TNF -α水平高于正常对照组 (P <0 0 5 ) ,术后两天排斥组与稳定组间尿液TNF -α水平无显著性差异 (P >0 0 5 )。 33例肾移植术后稳定者血清TNF -α水平术后 7天开始下降 ,至 2 1天时已降至与正常对照组无显著性差异 (P >0 0 5 ) ;尿液TNF -α水平下降较血清快 ,术后 7天即降至与正常对照组无显著性差异 (P >0 0 5 )。结论 :动态检测TNF -α水平可作为观察肾移植患者排斥反应的一项重要指标。     

肾移植受者血清TNF-α、IL-6和sIL-2R水平变化及临床意义

目的:探讨肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和可溶性白细胞介素-2受体(sIL-2R)在肾移植术后急性排斥反应中的变化。方法:采用固相酶标记化学发光免疫分析技术动态监测36例患者肾移植前后血清TNF-α、IL-6和sIL-2R水平,并结合临床资料作全面分析。结果:肾移植受者术后第1天血清TNF-α、IL-6和sIL-2R均明显升高,其中移植稳定组血清IL-6和sIL-2R第1天出现峰值后开始下降,而TNF-α则在术后5天达峰值后开始下降,至第10天均接近术前水平。急性排斥组血清TNF-α、IL-6和sIL-2R水平与肾功能稳定组比较,差异有显著性(P<0.05),抗排斥治疗有效后迅速下降。而环孢素A中毒组与稳定组比较,差异无显著性(P<0.05)。结论:肾移植术后受者血清TNF-α、IL-6和sIL-2R水平的检测,可在一定程度上反映肾移植受者的免疫反应状态,并为急性排斥反应的监测和诊断提供客观依据。     

白细胞介素-8研究进展

白细胞介素-8（IL-8）在趋化性细胞因子家族中属于C-X-C亚家族，IL-8是一个多种细胞来源的趋化性细胞因子，而且不同类型的细胞对不同的诱导剂的反应也不相同，因为由不同的实验室从不同的来源得到该因子，所以对于IL-8的许多不同的描述术语，对于IL-8的生理生化特性，目前已基本清楚，对于IL-8基因表达的调节，现认为主要是在转录水平的调控，并且发现其基因5′-侧翼区的AP-1，NF-кB及NF-IL-6结合位点是调节IL-8启动子功能的主要顺式作用元件，IL-8基因的表达需要这些元件之间高度的协同以达到有效的转录，IL-8受体则是一个由59KDa和67KDa亚单位组成的二聚体糖蛋白，存在于多种类型的细胞上，甚至包括一些不表达IL-8的细胞，IL-8的生物学活性并不表现出种族的特异性，IL-8可激活中性粒细胞，对T-淋巴细胞有趋化性并能刺激嗜碱性粒细胞，内皮细胞IL-8基因的表达除了受化学因子的调节外还受力学因素的影响，流体切应力诱导内皮细胞表达IL-8，可能在急性炎症和动脉粥样硬化的发生，发展过程中具有重要作用。     

The CD8 isoform CD8alphaalpha is not a functional homologue of the TCR co-receptor CD8alphabeta

Although structurally similar, CD8alphabeta and CD8alphaalpha have notably diverted with regard to function. Whereas CD8alphabeta functions as a T-cell receptor (TCR) co-receptor on MHC-class-I-restricted thymocytes and mature T cells, CD8alphaalpha is unable to support conventional positive selection, and can be expressed on T cells independent of the MHC restriction of their TCR. CD8alphaalpha induction is consistent with antigenic stimulation through the TCR, and recent developments have now shown that CD8alphaalpha induced on agonist-triggered immature thymocytes, antigenic-stimulated conventional CD8alphabeta T cells and mucosal T cells mediates the specific modulation of TCR activation signals to facilitate their survival and differentiation into various specialized T-cell subsets.     

Successful Conclusion of the 8th PPCTSS

Biglycan is a member of the family of small leucine-rich proteoglycans. It is an important structural component of articular cartilage and participates in the assembly of the chondrocyte extracellular matrix through formation of protein interactions with collagen type VI and large proteoglycan aggregates. Biglycan also possesses signaling properties. In articular chondrocytes, short-term activation of epidermal growth factor receptors (EGFR) with biglycan initiated mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3K) signaling events, similar to the effect of epidermal growth factor (EGF) observed in other cell types. The extent and duration of intracellular signaling resolves biological effects initiated by EGFR stimulation, thus, establishing cell fate. In this study, we elucidate a novel regulatory mechanism of EGFR expression in human articular chondrocytes that is modulated by prolonged biglycan treatment and is in contrast to changes detected in the expression of EGFR following EGF stimulation. Treatment of chondrocytes for 24 hr with biglycan upregulated EGFR mRNA and protein expression, whereas treatment with EGF downregulated EGFR message and protein levels. Biglycan and EGF treatment protracted extracellular signal-regulated kinases (ERK1/2) and Akt phosphorylation, albeit to different extents. Mechanistic studies with mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathway-specific inhibitors revealed that biglycan and EGF distinctly modulate the expression of EGFR in chondrocytes. Biglycan promoted the coactivation of ERK1/2 and Akt, however, phosphorylated Akt induced a prolonged inhibition of ERK1/2. Consequently, total EGFR mRNA and protein expression was increased. This regulatory mechanism contrasts the modulation of EGFR expression by exogenous EGF, which strongly protracts ERK1/2 activation, therefore, inducing a decrease of EGFR message and protein levels. Thus, biglycan might impinge on the expression of total EGFR and possibly, on the cell-surface expression of the receptors. These observations suggest that biglycan might play a critical role in the regulation of chondrocyte and pericellular matrix homeostasis.     

Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling

BACKGROUND: Members of the TGF-beta superfamily of ligands bind to and activate surface serine/threonine-kinase receptors. Transduction of these signals requires the Smad proteins, which transiently interact with the activated receptor complex and are phosphorylated on their C terminus, SSXS site, by the type I receptor. Smad8 is a downstream signalling mediator of ALK2/ActRIA. RESULTS: We have cloned a splice variant of Smad8, designated Smad8B. The Smad8 and Smad8B cDNAs are identical in sequence, except that Smad8B lacks a portion encoding 47 amino acids, including the SSXS phosphorylation site, in the C-terminal MH2 region. Both Smad8 and Smad8B were expressed in many of the same cell types. Smad8B was capable of specific complex formation with either Smad8 or Smad4 in mammalian cells. In cells expressing constitutively activated ALK2, Smad8B was localized to the cytoplasmic region, whereas Smad8 was translocated into the nucleus. In mammalian cells, Smad8B acted as a dominant inhibitor of BMP signalling. CONCLUSIONS: Smad8B, a splice variant of Smad8, was isolated and found to specifically associate with both Smad8 and Smad4. Smad8B inhibited BMP signalling. Smad8 and Smad8B thus represent novel signal transduction proteins that may regulate the BMP signalling pathway.     

Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways

BACKGROUND: CXCL8/IL-8 is the most significant chemokine for neutrophils, and CXC chemokine receptor (CXCR) 1 and 2 are its 2 receptors, which are downmodulated by CXCL8/IL-8 and endotoxin on activated neutrophils. OBJECTIVE: We sought to evaluate the expression of the CXCL8/IL-8 receptors and the activation marker CD11b on neutrophils in peripheral blood and in the site of airway inflammation. METHODS: The flow cytometric expression of CXCR1, CXCR2, and CD11b was evaluated on peripheral blood and induced sputum neutrophils in patients with nonsevere asthma with greater than 60% sputum neutrophils, in patients with chronic obstructive pulmonary disease (COPD), and in healthy control subjects. RESULTS: Asthmatic patients and patients with COPD had comparable expressions of CXCR1, CXCR2, and CD11b on peripheral blood and sputum neutrophils. Compared with control subjects, the peripheral neutrophil expression of CXCR2 was lower in patients with COPD ( P = .03) and that of CD11b was higher in asthmatic patients and patients with COPD ( P < .02 and P < .002). The expression of the CXCL8/IL-8 receptors on sputum neutrophils was markedly lower than on peripheral blood neutrophils ( P < .0001). The downmodulation of CXCL8/IL-8 receptors was also present in healthy control subjects but less than that seen in asthmatic patients. The difference between peripheral blood and sputum expression of CXCL8/IL-8 receptors correlated with serum CXCL8/IL-8 levels. In asthmatic patients the expression of CXCR1 and CXCR2 on sputum neutrophils negatively correlated with sputum neutrophils. CONCLUSION: In neutrophilic asthma the expression of CXCL8/IL-8 receptors on peripheral and sputum neutrophils is similar to COPD and negatively correlated with the inflammatory infiltrate in the airways. The downmodulation of CXCL8/IL-8 receptors detected in the airways should be taken into account for an eventual therapeutic inhibition of these receptors.     

The emerging role of the human herpesvirus 8 (HHV8) in human neoplasia

The human herpesvirus 8 (HHV8) was initially described and characterised in Kaposi's sarcoma tissue. The virus was found in the lesion of most cases of Kaposi's sarcoma. Whilst there is a large body of evidence to implicate its role in the pathogenesis of Kaposi's sarcoma, it has recently been found that the virus may also be important in a number of other human neoplasias. This review will examine the molecular pathology of HHV8 in the pathogenesis of Kaposi's sarcoma and summarise the current evidence and postulated mechanisms in its role in other human neoplasias.     

Trisomy of chromosome 8 in myelodysplastic syndrome. Significance of the fluctuating trisomy 8 population.

Chromosome analyses were performed in five patients with myelodysplastic syndrome (MDS) who showed trisomy of chromosome 8 during the course of their disease. Four of these patients showed trisomy 8 at the diagnosis of MDS, and the remaining one had trisomy 8 when the leukemia phase developed. The proportion of bone marrow (BM) cells with trisomy 8 in the four patients who showed trisomy 8 at MDS diagnosis fluctuated, and this fluctuation was not related to the percentage of blasts in the BM or to progression of the disease. However, in two patients, metaphase cells with trisomy 8 disappeared when their anemic state improved, although leuko-thrombocytopenia was still present, suggesting that the decrease in the number of BM cells with trisomy 8 reflects hematologic features in some MDS patients. These findings indicate that trisomy 8 in our MDS patients was possibly not the primary event in the genesis of the disease, and that there may have been competition between a normal karyotype clone and a trisomy-8-positive clone. Our results further suggest that the presence of a clone with trisomy 8 is not always a sign of disease progression or of poor prognosis in MDS patients.     

Mosaicism and the trisomy 8 syndrome

Three new cases of trisomy 8 mosaicism are presented; two have features corresponding with those usually found in this syndrome, whereas one is highly atypical.
In view of the almost universal mosaicism of these patients, the literature is reviewed with an emphasis on the patterns of mosaicism found. There is little correlation between degree of mosaicism and extent of clinical abnormality. The degree of mosaicism differs in different tissues, fibroblasts being more informative of aneuploidy than lymphocytes, and there is some evidence that the degree of mosaicism varies with time. The reasons for these findings are discussed, with particular reference to the raised paternal age found in a proportion of the reported cases.     

DOCK8 is essential for T-cell survival and the maintenance of CD8+ T-cell memory

Deficiency in the guanine nucleotide exchange factor dedicator of cytokinesis 8 (DOCK8) causes a human immunodeficiency syndrome associated with recurrent sinopulmonary and viral infections. We have recently identified a DOCK8‐deficient mouse strain, carrying an ethylnitrosourea‐induced splice‐site mutation that shows a failure to mature a humoral immune response due to the loss of germinal centre B cells. In this study, we turned to T‐cell immunity to investigate further the human immunodeficiency syndrome and its association with decreased peripheral CD4⁺ and CD8⁺ T cells. Characterisation of the DOCK8‐deficient mouse revealed T‐cell lymphopenia, with increased T‐cell turnover and decreased survival. Egress of mature CD4⁺ thymocytes was reduced with increased migration of these cells to the chemokine CXCL12. However, despite the two‐fold reduction in peripheral naïve T cells, the DOCK8‐deficient mice generated a normal primary CD8⁺ immune response and were able to survive acute influenza virus infection. The limiting effect of DOCK8 was in the normal survival of CD8⁺ memory T cells after infection. These findings help to explain why DOCK8‐deficient patients are susceptible to recurrent infections and provide new insights into how T‐cell memory is sustained.