自身免疫机制与心血管疾病关系的研究进展

自身免疫是人们在正常环境下,免疫系统仅仅对自身以外的其他异物抗原发生的某种反应,由于特殊原因对自身构成发起攻击引起的反应。经自身免疫机制以及心血管疾病发病机制的研究表明,自身免疫机制与多种心血管疾病的发病有着密切联系,并且加快了心肌病、心血管炎性疾病、高血压性心脏病、心力衰竭以及心肌梗死等疾病的发展。

Modulation of cellular and humoral immune responses to anHIV-1 DNA vaccine by interleukin-12 and interleukin-18 DNA immunization

Objective: To investigate the effect of interleukin-12 (IL-12) and interleukin-18 (IL-18)DNA immunization on immune response induced by HIV-1 DNA vaccine and to explore new strategies for therapeutic HIV DNA vaccine. Methods: The recombinant expression vector pCI-neoGAG was constructed by inserting HIV Gag gene into the eukaryotic expression vector pCI-neo. Balb/c mice were immunized with pCI-neoGAG alone or co-immunized with the DNA encoding for IL-12 or IL-18.Anti-HIV antibody and IFN-γ were tested by ELISA,and splenocytes were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay respectively. Results: The anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 were lower than that of mice immunized with pCI-neoGAG alone(P<0.01). In contrast, the IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 was higher than that of mice immunized with pCI-neoGAG alone (P<0.01).Furthermore, compared with mice injected with pCI-neoGAG alone, the specific CTL cytotoxity activity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 were significantly enhanced respectively (P<0.01). Conclusion: The DNA encoding for IL-12 or IL-18 together with HIV DNA vaccine may enhance specific Th-1 responses and cellular immune response elicited in mice. Hence, the DNA encoding for IL-12 or IL-18 are promising immune adjuvants for HIV-1 DNA vaccine.

Potent T cell Responses Induced by Single DNA Vaccine Boosted with Recombinant Vaccinia Vaccine

Plasmid DNA, an effective vaccine vector, can induce both cellular and humoral immune responses. However, plasmid DNA raises issues concerning potential genomic integration after injection. This issue should be considered in preclinical studies. Tiantan vaccinia virus (TV) has been most widely utilized in eradicating smallpox in China. This virus has also been considered as a successful vaccine vector against a few infectious diseases. Potent T cell responses through T-cell receptor (TCR) could be induced by three injections of the DNA prime vaccine followed by a single injection of recombinant vaccinia vaccine. To develop a safer immunization strategy, a single DNA prime followed by a single recombinant Tiantan vaccinia (rTV) AIDS vaccine was used to immunize mice. Our data demonstrated that one DNA prime/rTV boost regimen induced mature TCR activation with high functional avidity, preferential T cell Vβ receptor usage and high sensitivity to anti-CD3 antibody stimulation. No differences in T cell responses were observed among one, two or three DNA prime/rTV boost regimens. This study shows that one DNA prime/rTV boost regimen is sufficient to induce potent T cell responses against HIV.

Requirement for cyclin D3 in germinal center formation and function

Germinal centers （GC） of secondary lymphoid tissues are critical to mounting a high-affinity humoral immune response. B cells within the GC undergo rapid clonal expansion and selection while diversifying their antibody genes. Although it is generally believed that GC B cells employ a unique proliferative program to accommodate these processes, little is known about how the GC-associated cell cycle is orchestrated. The D-type cyclins constitute an important component of the cell cycle engine that enables the cells to respond to physiological changes. Cell type- and developmental stage-specific roles of D-type cyclins have been described but the cyclin D requirement during GC reaction has not been addressed. In this study, we report that cyclin D3 is largely dispensable for proliferation and Ig class switching of in vitro activated B cells. In contrast, GC development in Ccnd3^-/- mice is markedly impaired, as is the T cell-dependent antibody response. Within the GC, although both switched and unswitched B cells are affected by cyclin D3 inactivation, the IgM^- pool is more severely reduced. Interestingly, despite a compensatory increase in cyclln D2 expression, a significant number of Ccnd3^-/- GC B cells accumulate in quiescent GO state. Lastly, although cyclin D3 inactivation did not disrupt BCL6 expression in GC B cells, it completely blocked the GC promoting effect of BCL6 overexpression, suggesting that cyclin D3 acts downstream of BCL6 to regulate GC formation. This is the first demonstration that cyclin D3 plays an important and unique role at the GC stage of B cell development.

Effects of the Aidi Dripping Pills on Immune Functions of the Tumor-bearing Mouse

Objective： To study the effects of Aidi Dripping Pills on immune functions of the tumor-bearing mouse on the basis of the previous experimental studies on its tumor-inhibiting and life-prolonging effects. Methods： By using the transplantation tumor mouse models, the effects of Aidi Dripping Pills on the lymphocyte transformation rate and the hemolysin formation in the Sis0 tumor-bearing mice, and on the phagocytic function of macrophages in the abdominal cavity of H22 tumor-bearing mice were investigated. Results： In the 2.25 g/kg and 1.125 g/kg Aidi Dripping Pills groups, the lymphocyte transformation rates in the Sis0 tumor-bearing mice were significantly higher than that of the control group （P〈0.01）. In all the Aidi Dripping Pills groups, HC50 significantly increased （P〈0.01 or P〈0.05）, carbon granular clearance significantly raised, and both the phagocytic index and phagocytic coefficient were significantly higher than those in the control group （P〈0.01 or P〈0.05）. Conclusion： The Aidi Dripping Pills can significantly increase the cellular immune function, the humoral immune function and the phagocytic function of the mononuclear- macrphages, so it may show anti-tumor effects by enhancing the function of the reticuloendothelial system.

Establishing guidelines for CAR-T cells： challenges and considerations

T cells, genetically modified by chimeric antigen receptors(CAR-T), are endowed with specificity to a desired antigen and are cytotoxic to cells expressing the targeted antigen. CAR-T-based cancer immunotherapy is a promising therapy for curing hematological malignancy, such as acute lymphoid leukemia, and is promising for extending their efficacy to defeat solid tumors. To date, dozens of different CAR-T cells have been evaluated in clinical trials to treat tumors; this necessitates the establishment of guidelines for the production and application of CAR-T cells. However, it is challenging to standardize CAR-T cancer therapy because it involves a combination of gene therapy and cell therapy. In this review, we compare the existing guidelines for CAR-T cells and discuss the challenges and considerations for establishing guidance for CAR-T-based cancer immunotherapy.

Global stability of a delayed virus dynamics model with multi-staged infected progression and humoral immunity

In this paper, we propose a nonlinear virus dynamics model that describes the interac- tions of the virus, uninfected target cells, multiple stages of infected cells and B cells and includes multiple discrete delays. We assume that the incidence rate of infection and removal rate of infected cells are given by general nonlinear functions. The model can be seen as a generalization of several humoral immunity viral infection model presented in the literature. We derive two threshold parameters and establish a set of conditions on the general functions which are sufficient to establish the existence and global stability of the three equilibria of the model. We study the globa! asymptotic stability of the equilibria by using Lyapunov method. We perform some numerical simulations for the model with specific forms of the general functions and show that the numerical results are consistent with the theoretical results.