IL-21在滤泡辅助性T细胞分化发育及功能中的作用

抗原刺激B细胞产生抗体需要T细胞辅助,近年来人们逐渐认识到一个命名为滤泡辅助性T细胞（Tfh）的CD4^＋T细胞亚群在B细胞诱导的免疫应答中具有重要作用。Tfh细胞的主要特征包括表达趋化因子受体与（CXCR5）,迁移定位于B细胞滤泡辅助B细胞产生抗体。Tfh细胞产生的细胞因子IL-21能够促进B细胞分化为抗体形成细胞,这种辅助性细胞因子在Tfh细胞的分化发育、效应发挥及Tfh细胞功能失调相关的疾病中具有重要意义。     

IL-21在滤泡辅助性T细胞分化发育及功能中的作用

抗原刺激B细胞产生抗体需要T细胞辅助,近年来人们逐渐认识到一个命名为滤泡辅助性T细胞(Tfh)的CD4+T细胞亚群在B细胞诱导的免疫应答中具有重要作用.Tfh细胞的主要特征包括表达趋化因子受体与(CXCR5),迁移定位于B细胞滤泡辅助B细胞产生抗体.Tfh细胞产生的细胞因子IL-21能够促进B细胞分化为抗体形成细胞,这种辅助性细胞因子在Tfh细胞的分化发育、效应发挥及Tfh细胞功能失调相关的疾病中具有重要意义.     

滤泡辅助性T细胞与自身免疫病

滤泡辅助性T细胞(Tfh)是近年来被确认的新的CD4~+辅助性T细胞亚群,主要功能是刺激B细胞增殖、分化和辅助B细胞产生相应抗体以及诱导生发中心(GC)形成。Tfh发育或功能异常会诱发异常的体液免疫引起自身免疫病发生。     

滤泡辅助性T细胞在HIV感染及疫苗免疫中的作用及机制

滤泡辅助性T细胞( follicular helper T cell, Tfh )是近期发现的具有B细胞辅助功能的CD4+T淋巴细胞亚群, 对于生发中心形成、亲和力成熟、高亲和力抗体产生和记忆B细胞的发育至关重要。Tfh与艾滋病(acquired immunodeficiency syndrome, AIDS)发展进程密切相关。在人类免疫缺陷病毒(human immunodeficiency virus, HIV)感染过程中, Tfh细胞数量、功能、病毒潜伏、Tfh/滤泡调节T细胞(follicular regulatory T cell, Tfr)比例平衡、中和抗体产生等方面均发生变化。文章综述Tfh在HIV感染及疫苗免疫后抗体应答中的作用及机制, 旨在为HIV疫苗的设计与免疫策略制定提供参考。     

滤泡调节性T细胞在病毒感染与疫苗免疫中的作用及机制研究进展

滤泡调节性T细胞(T follicular regulatory cell,Tfr)是近年来发现的一类CD4⁺T细胞亚群,其来源于调节性T细胞(T regulatory cell,Treg),兼具Treg细胞及滤泡辅助性T细胞(T follicular helper cell,Tfh)相似的生物学特征。Tfr细胞在次级淋巴器官生发中心(germinal center,GC)调控Tfh细胞和B细胞的分化,辅助筛选高亲和力抗体,并防止自身抗体产生,确保免疫平衡。本文通过综述Tfr细胞的生物学特征和功能,总结Tfr细胞在病毒感染及疫苗免疫后抗体应答中的作用,旨在深刻理解病毒感染后抗体产生和成熟的免疫调节机制,为病毒疫苗的设计与免疫策略制定提供参考。     

滤泡辅助性T细胞在器官移植免疫中的研究进展

滤泡辅助性T(Tfh)细胞是从人类扁桃体中发现的一类辅助性T(Th)细胞,Tfh细胞通过分泌白细胞介素21(IL-21)促进B细胞分化为浆母细胞,产生免疫球蛋白并促进生发中心形成。抗体介导的体液排异反应是移植物功能丧失的重要原因,而抗体的产生有赖于Tfh细胞的辅助,并且IL-21受体的抑制剂抑制Tfh细胞和B细胞在同种异体反应中的功能。本文将对近年来Tfh细胞在分化、亚型及器官移植中在抗体介导的排异反应中的作用进行综述,并推测其在未来移植后发生体液免疫排异患者中的意义。     

滤泡辅助性T细胞与淋巴瘤关系的研究进展

滤泡辅助性T细胞(follicular helper T cells,TFH)是近年来发现的一种新的辅助T细胞亚群,由Schaerli等[1]首先报道了一个定位于淋巴滤泡、具有辅助B细胞功能、表型为CXCR5+ CD40L+ ICOS+的T细胞亚群,称为滤泡B辅助性T细胞.此后经过大量研究,直到最近TFH才被正式确定[2].目前认为TFH是一种具有独特功能的新的辅助T细胞亚群,TFH稳定表达趋化因子受体(CXCR)5,使之迁移至淋巴滤泡,与B淋巴细胞相互作用,并辅助B淋巴细胞产生抗体,同时TFH高表达白细胞介素(IL)-21、ICOS、bcl-6.目前证实血管免疫母细胞T细胞淋巴瘤(AITL)来源于TFH,而且TFH与滤泡性淋巴瘤微环境密切相关,无疑TFH与某些淋巴瘤关系的发现和证实是近年来淋巴瘤研究的一个重要进展.本文对于TFH与淋巴瘤发生之间的研究进展做一综述.     

滤泡辅助性T细胞及其可塑性的研究进展

初始T细胞受到抗原刺激后,在不同细胞因子的调控下,分化成不同的CD4+T细胞亚群,主要包括Th1、Th2、Th17、Treg和Tfh细胞。滤泡辅助性T细胞(follicular helper T cell,Tfh)是一类新的CD4+T细胞亚群,参与生发中心(germinal center,GC)形成,促使B细胞分化成浆细胞和记忆B细胞,进而在产生抗体的过程中发挥着重要作用。研究发现,Tfh细胞与其他辅助性T细胞在表达转录因子和产生细胞因子上具有重叠性,并且具有向其他CD4+T细胞亚群分化的潜能。本文主要综述Tfh细胞分化的相关分子以及表现Tfh细胞可塑性的证据。     

Tfh与Tfr的研究进展及其在类风湿性关节炎发展中的作用

滤泡辅助性T细胞(follicular helper T cell,Tfh)和滤泡调节性T细胞(follicular regulatory T cell,Tfr)是近年新发现的两种重要的T细胞类型,它们对促进生发中心(germinal center,GC)形成、B细胞发育及高亲和抗体产生具有重要作用。类风湿性关节炎(rheumatoid arthritis,RA)是一种常见的慢性系统性自身免疫性疾病,以关节滑囊组织炎症和关节退化为主要特征,同时存在多种自身反应性抗体的异常表达。本文综述Tfh与Tfr的分化与分子标志及主要功能的研究进展,阐述两种细胞在RA发展中的可能作用。     

滤泡辅助性T细胞在免疫相关性血液病中的研究进展

T细胞亚群异常是导致免疫相关性血液病发病的重要因素,其发病机制与Thl／Th2、Thl7细胞、调节性T细胞（Treg）等辅助性T细胞异常有关。滤泡辅助性T细胞（Tfh）作为新近发现的辅助性T细胞具有辅助B细胞产生抗体的作用,其产生、分化和功能均不同于以往的Thl、Th2和Thl7等CD4＋T细胞。Tfh细胞及其相关分子的数量和／或功能异常在免疫相关性血液病的发病中发挥重要作用,有望成为其新的治疗靶点。     

Pain and Effusion and Quadriceps Activation and Strength

Context:

Quadriceps dysfunction is a common consequence of knee joint injury and disease, yet its causes remain elusive.

Objective:

To determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion affect the magnitude of quadriceps dysfunction.

Design:

Crossover study.

Setting:

University research laboratory.

Patients or Other Participants:

Fourteen (8 men, 6 women; age = 23.6 ± 4.8 years, height = 170.3 ± 9.16 cm, mass = 72.9 ± 11.84 kg) healthy volunteers.

Intervention(s):

All participants were tested under 4 randomized conditions: normal knee, effused knee, painful knee, and effused and painful knee.

Main Outcome Measure(s):

Quadriceps strength (Nm/kg) and activation (central activation ratio) were assessed after each condition was induced.

Results:

Quadriceps strength and activation were highest under the normal knee condition and differed from the 3 experimental knee conditions (P < .05). No differences were noted among the 3 experimental knee conditions for either variable (P > .05).

Conclusions:

Both pain and effusion led to quadriceps dysfunction, but the interaction of the 2 stimuli did not increase the magnitude of the strength or activation deficits. Therefore, pain and effusion can be considered equally potent in eliciting quadriceps inhibition. Given that pain and effusion accompany numerous knee conditions, the prevalence of quadriceps dysfunction is likely high.Key Words: arthrogenic muscle inhibition, central activation failure, voluntary activation, muscles

Key Points

• Knee pain and effusion resulted in arthrogenic muscle inhibition and weakness of the quadriceps.
• The simultaneous presence of pain and effusion did not increase the magnitude of quadriceps dysfunction.
• To reduce arthrogenic muscle inhibition and improve muscle strength, clinicians should employ interventions that target removing both pain and effusion.

Quadriceps weakness is a common consequence of traumatic knee joint injury^1,2 and chronic degenerative knee joint conditions.^3,4 Arthrogenic muscle inhibition (AMI), a neurologic decline in muscle activation, results in quadriceps weakness and hinders rehabilitation by preventing gains in strength.⁵ The inability to reverse AMI and restore muscle function can lead to decreased physical abilities,⁶ biomechanical deficits,⁷ and possibly reinjury.⁵ Furthermore, researchers^8,9 have suggested that quadriceps weakness resulting from AMI may place patients at risk for developing osteoarthritis in the knee. In light of the substantial influence of quadriceps AMI on these clinically relevant outcomes, we need to improve our understanding of the factors that contribute to this neurologic decline in muscle activity so efforts to target and reverse it can be implemented and gains in strength can be achieved more easily.Joint injury and disease are accompanied by numerous sequelae (ie, pain, swelling, tissue damage, inflammation), so ascertaining which one ultimately leads to neurologic muscle dysfunction is difficult. Whereas a joint effusion can result in AMI,^10–12 the effects of pain are less understood despite many clinicians attributing AMI to pain. Using techniques that introduce knee pain without accompanying injury may provide insights into the role of pain in eliciting AMI.The degree of knee joint damage may play a role in the quantity of AMI that manifests. Hurley et al^13,14 demonstrated that quadriceps AMI, measured using an interpolated-twitch technique, was greater in patients with extensive traumatic knee injury (eg, fractured tibial plateau, ruptured medial collateral ligament, and medial meniscectomy) than patients with isolated joint trauma (ie, isolated anterior cruciate ligament [ACL] rupture). Similarly, patients with more knee joint symptoms (ie, greater number of symptoms and increased severity of symptoms) may present with greater magnitudes of quadriceps inhibition. Recently, investigators¹⁵ have suggested that patients with more pain display less quadriceps strength, supporting this tenet. Given that effusion and pain often present simultaneously with joint injuries and diseases, such as ACL injury and osteoarthritis, examining both the isolated and cumulative effects of these sequelae appears warranted to determine if they influence the magnitude of muscle inhibition.Experimental joint-effusion and pain models are safe and effective experimental methods that allow for the isolated examination of their effects on muscle function. The effusion model, whereby sterile saline is injected directly into the knee joint capsule,⁷ produces a clinically relevant magnitude of the joint effusion that may be present with traumatic injury. Effusion is thought to activate group II afferents responding to stretch or pressure,^16–18 which in turn may facilitate group Ib interneurons and result in quadriceps AMI.⁵ The pain model involves injecting hypertonic saline into the infrapatellar fat pad to produce anteromedial knee pain similar to that described in patients with patellofemoral pain syndrome.¹⁹ Pain is considered to initiate AMI through activation of group III and IV afferents that act as nocioceptors to signal damage or potential damage to joint structures.^16–18 The firing of these afferents then may lead to facilitation of group Ib interneurons, the flexion reflex, or the gamma loop, ultimately resulting in quadriceps inhibition.²⁰ Thus, these models allow us to create symptoms that are associated with knee injury and have the added benefit of providing a way to examine their effects in isolation.Therefore, the purpose of our study was to determine the effects of pain on quadriceps strength and activation and to learn if simultaneous pain and knee joint effusion would affect the magnitude of quadriceps dysfunction. We hypothesized that pain alone would result in quadriceps inhibition and that the magnitude of inhibition would be greater when effusion and pain were present simultaneously.     

即早基因c-fos与脑血管病及学习记忆

即早基因c-fos是广泛存在于原核细胞和真核细胞的高度保守基因.在正常情况下,c-fos基因参与细胞生长、分化、信息传递、学习和记忆等生理过程,而在病理情况下c-fos基因表达及调控变化与多种疾病的发生和发展有关.C-fos在中枢神经系统的某些部位可有基础水平的表达,但表达很低,当受到如脑缺血、脑出血、痫性发作、应激等刺激后,其在数十分钟内做出反应,在对外界刺激-转录耦联的信忠传递过程中起着核内第三信使的重要作用.     

Opportunities and challenges in the prevention and control of cancer and other chronic diseases: children's diet and nutrition and weight and physical activity

OBJECTIVE: The purpose of this article is to review the role of behavioral research in disease prevention and control, with a particular emphasis on lifestyle- and behavior-related cancer and chronic disease risk factors--specifically, relationships among diet and nutrition and weight and physical activity with adult cancer, and tracking developmental origins of these health-promoting and health-compromising behaviors from childhood into adulthood. METHOD: After reviewing the background of the field of cancer prevention and control and establishing plausibility for the role of child health behavior in adult cancer risk, studies selected from the pediatric published literature are reviewed. Articles were retrieved, selected, and summarized to illustrate that results from separate but related fields of study are combinable to yield insights into the prevention and control of cancer and other chronic diseases in adulthood through the conduct of nonintervention and intervention research with children in clinical, public health, and other contexts. RESULTS: As illustrated by the evidence presented in this review, there are numerous reasons (biological, psychological, and social), opportunities (school and community, health care, and family settings), and approaches (nonintervention and intervention) to understand and impact behavior change in children's diet and nutrition and weight and physical activity. CONCLUSIONS: Further development and evaluation of behavioral science intervention protocols conducted with children are necessary to understand the efficacy of these approaches and their public health impact on proximal and distal cancer, cancer-related, and chronic disease outcomes before diffusion. It is clear that more attention should be paid to early life and early developmental phases in cancer prevention.