Vaccination against atherosclerosis: An overview

Atherosclerosis, an inflammatory disorder involving innate and adaptive immune responses with both atheroprotective and proatherogenic roles, is a life wasting and economic demanding disorder that continues to be the leading cause of morbidity and mortality worldwide. Thus, the need for a long-lasting and highly effective treatment has made researchers to find new strategies. Many efforts made thus far to reduce the burden of the disease have been toward the modification of cardiovascular risk factors.Vaccination against atherosclerosis has been investigated as a promising strategy to overcome the disorder. Several kinds of vaccination methods have been investigated mostly in mice, with promising results in the attenuation of atherosclerosis, inflammation, and lipid concentration. The most conflicting part of this strategy is finding appropriate antigens and adjuvants. Some antigens have been used, including OxLDL, apoB100, CETP, PCSK9, HSP60, MHC-II-derived peptides, and interleukins. The DNA-based vaccination method has opened a new window in this field. There is an increasing necessity for developing an effective, economical, long-lasting, accessible, and convenient vaccination method. There are large gaps in evidence for the selection of proper human sampling to test the vaccines, route of delivery, safety, strength, scheduling, and side effects, all of which must be considered in clinical trials in the future.     

The DNA damage response induces antigen presenting cell‐like functions in fibroblasts

The DNA damage response (DDR) alerts the immune system to the danger posed by DNA damage through the induction of damage‐associated molecular pattern molecules, chemokines, and ligands for activating immune receptors such as lymphocyte function‐associated antigen 1 (LFA‐1), NKG2D, and DNAX accessory molecule 1 (DNAM‐1). Here we provide evidence that OVA^257–264‐pulsed fibroblasts gain the ability to activate naïve OT‐I CD8⁺ T cells in response to DNA damage. The ability of fibroblasts to activate OT‐I CD8⁺ T cells depended on the upregulation of ICAM‐1 on fibroblasts and DNAM‐1 expression of CD8⁺ T cells. OVA^257–264‐pulsed fibroblasts were able to induce a protective T‐cell response against B16‐OVA cells in a DDR‐dependent manner. Hence, the DDR may alert the immune system to the presence of potentially dangerous cells by upregulating the expression of ligands that can induce the activation of innate and adaptive immune cells.     

Vγ9Vδ2 TCR‐activation by phosphorylated antigens requires butyrophilin 3 A1 (BTN3A1) and additional genes on human chromosome 6

Pyrophosphorylated metabolites of isoprenoid‐biosynthesis (phosphoantigens, PAgs) activate Vγ9Vδ2 T cells during infections and trigger antitumor activity. This activation depends on expression of butyrophilin 3 A1 (BTN3A1) by antigen‐presenting cells. This report defines the minimal genetic requirements for activation of Vγ9Vδ2 T cells by PAgs and mAb 20.1. We compared PAg‐presentation by BTN3A1‐transduced CHO hamster cells with that of CHO cells containing the complete human chromosome 6 (Chr6). BTN3A1 expression alone was sufficient for activation of Vγ9Vδ2 T‐cell receptor transductants by mAb 20.1., while activation by PAgs also required the presence of Chr6. We take this finding as evidence that gene(s) on Chr6 in addition to BTN3A1 are mandatory for PAg‐mediated activation of Vγ9Vδ2 T cells. This observation is important for the design of animal models for PAg‐mediated immune responses and provokes speculations about the analogy between genes controlling PAg presentation and MHC‐localized genes controlling peptide‐antigen presentation.     

A novel T‐cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice

We used a newly generated T‐cell receptor mimic monoclonal antibody (TCRm MAb) that recognizes a known nonself immunodominant peptide epitope from West Nile virus (WNV) NS4B protein to investigate epitope presentation after virus infection in C57BL/6 mice. Previous studies suggested that peptides of different length, either SSVWNATTAI (10‐mer) or SSVWNATTA (9‐mer) in complex with class I MHC antigen H‐2D^b, were immunodominant after WNV infection. Our data establish that both peptides are presented on the cell surface after WNV infection and that CD8⁺ T cells can detect 10‐ and 9‐mer length variants similarly. This result varies from the idea that a given T‐cell receptor (TCR) prefers a single peptide length bound to its cognate class I MHC. In separate WNV infection studies with the TCRm MAb, we show that in vivo the 10‐mer was presented on the surface of uninfected and infected CD8α⁺CD11c⁺ dendritic cells, which suggests the use of direct and cross‐presentation pathways. In contrast, CD11b⁺CD11c^? cells bound the TCRm MAb only when they were infected. Our study demonstrates that TCR recognition of peptides is not limited to certain peptide lengths and that TCRm MAbs can be used to dissect the cell‐type specific mechanisms of antigen presentation in vivo.     

The WT hemochromatosis protein HFE inhibits CD8+ T‐lymphocyte activation

MHC class I (MHC I) antigen presentation is a ubiquitous process by which cells present endogenous proteins to CD8⁺ T lymphocytes during immune surveillance and response. Hereditary hemochromatosis protein, HFE, is involved in cellular iron uptake but, while structurally homologous to MHC I, is unable to bind peptides. However, increasing evidence suggests a role for HFE in the immune system. Here, we investigated the impact of HFE on CD8⁺ T‐lymphocyte activation. Using transient HFE transfection assays in a model of APCs, we show that WT HFE (HFE_WT), but not C282Y‐mutated HFE, inhibits secretion of MIP‐1β from antigen‐specific CD8⁺ T lymphocytes. HFE_WT expression also resulted in major decreases in CD8⁺ T‐lymphocyte activation as measured by 4–1BB expression. We further demonstrate that inhibition of CD8⁺ T‐lymphocyte activation was independent of MHC I surface levels, β2‐m competition, HFE interaction with transferrin receptor, antigen origin, or epitope affinity. Finally, we identified the α1–2 domains of HFE_WT as being responsible for inhibiting CD8⁺ T‐lymphocyte activation. Our data imply a new role for HFE_WT in altering CD8⁺ T‐lymphocyte reactivity, which could modulate antigen immunogenicity.     

Reactive arthritis induced by intravesical BCG therapy for bladder cancer: our clinical experience and systematic review of the literature

Objective

Intravesical instillation of BCG (ivBCG) is an effective and safe immunotherapy of bladder carcinoma but it may have, as side effect, a reactive arthritis (ReA). The authors describe 5 cases observed during their own clinical experience along with the updated review of the literature on this topic.

Methods

Seventy-three papers were present in the world literature, each reporting almost 1 case for a total of 112 patients. However, the review focused on 61 papers, selected on the basis of reporting suitable for a correct clinical evaluation; thus, a total of 89 patients, including the cases observed in our clinic, were carefully analyzed.

Results

Among the 89 patients identified 73 were males and 16 females. Europe is the geographical area with the higher number of reports, namely 80.6% of the papers including 74.2% of the patients. The Mediterranean area accounts for 62.9% of the papers and 59.6% of the cases. The symptoms of ReA appeared after a mean number of instillations of 5.8. Polyarthritis was present in 55.1%, oligoarthritis in 37.0% and monoarthritis in 7.9%. Polyarthritis was symmetric in 51.0% and asymmetric in 49.0% of the cases; oligoarthritis was symmetric in 33.3% and asymmetric in 66.7% of the cases. Overall, an asymmetric distribution of arthritis was present in 59.6%. Knee and ankle were the joints most frequently involved. The antigen HLA B27 was positive in 42.6%. The synovial fluid analysis was defined as flogistic–aseptic in 71.9% of the patients. Arthritis was recovered within 6 months in 93.2% of the cases and in 70.5% of the patients within the first two months. NSAIDs and corticosteroids, alone or in conjunction with other drugs, are used in 65.1% and in 40.4% of the cases, respectively. The clinical features of ivBCG ReA are compared with ReA from other triggering agents, from which it differs for some clinical aspects and overlaps for others.

Conclusions

Compared with a previous report, this review allows to modify some figures of this topic as a reduced prevalence of polyarthritis (from 70% to 55.1%) and of spinal and sacroiliac involvement; polyarthritis remains the more frequent clinical pattern of ivBCG ReA that, however, is characterized by rather asymmetrical distribution and involvement of the large joints of lower limbs. A definite linkage to HLA B27 is present, although without prognostic value. Moreover, arthritis is aseptic, has a latency time from antigen exposure, and is associated with extra-articular features as commonly observed in ReA from other triggering agents. Arthritis is usually benign and rarely develops into a chronic form. NSAIDs and/or corticosteroids are largely effective. Noteworthy, the overall clinical picture of arthritis triggered by ivBCG emerging from this updated review is comparable to that of ReA from other bacterial agents.     

日本血吸虫病诊断抗原研究进展

血吸虫病免疫诊断技术的发展为血吸虫病控制做出了重要贡献。血吸虫抗原检测特异性抗体是目前血吸虫病免疫诊断的常用方法,所使用的抗原可分为粗制虫源抗原、纯化虫源抗原和重组抗原。研制高敏感性、高特异性和具有早期诊断价值的抗原是免疫诊断研究的重点。本文对近年日本血吸虫病诊断抗原研究进展进行了综述。     

抗凝与非抗凝血标本对ELISA检测血清乙肝表面抗原的影响

目的 探讨抗凝与非抗凝血液标本对乙肝表面抗原酶联免疫吸附试验(ELASA)检测结果是否存在差别.方法 留取160人份血标本各2管,分别经枸橼酸-枸橼酸钠抗凝及非抗凝,进行平行实验.结果 160人份标本的平行试验,部分项目结果差异有统计学意义(P＜0.05).结论 采用枸橼酸-枸橼酸钠抗凝血标本,对乙肝表面抗原检测结果存在着一定干扰,采用抗凝血标本进行ELASA检测对试验结果是否有影响已被同行广泛关注.     

抗原优势表位的筛选方法

疫苗的出现有效降低了人类感染性疾病的发病率和死亡率。随着科学的进步和发展,发现原始的疫苗已经不能满足当今社会的需要。现代保护性免疫理论认为,有效的保护性免疫来源于一组表位的合理组合与搭配。近年来兴起的表位研制技术,是用抗原表位制备疫苗,它在感染性疾病和恶性肿瘤中有着自身独特的优势。因此如何在众多的表位中确定优势表位,已经成为研究的新方向。本文详细阐述了优势表位的筛选办法,对其最新的研究进展进行了综述。