Recognition of a novel naturally processed, A2 restricted, HCV-NS4 epitope triggers IFN-gamma release in absence of detectable cytopathicity

Using short term CTL lines derived from HLA A2/K^b transgenic mice and IFN-gamma release assays we demonstrate that the NS4.1769 epitope, is generated from natural processing of the NS4 antigen, and presented in the context of the A2/K^b molecules. Interestingly, T cell recognition of the naturally processed form of the NS4.1769 epitope was associated with significant IFN-gamma release, but no direct cytolytic activity. Epitopes of this phenotype might be of interest, in terms of therapy of chronic HCV infection by associating the benefit of localized lymphokine release with low or absent direct cytopathicity.     

Astrocytes and intracerebral immune responses

The astrocyte is the most abundant cell within the central nervous system (CNS). This cell subserves a multiplicity of important functions that contribute to the process of neural development as well as to the integrity of normal brain function. Adding to the already exhaustive list of capabilities, the astrocyte has now been demonstrated to function as an intracerebral antigen presenting cell. These findings are serving to revise our view of the brain as an immunoprivileged site and perhaps will shed some light on the pathogenetic mechanisms involved in a number of CNS disorders of immune dysregulation. In this review we provide some perspective on the regulatory mechanisms that influence astrocyte immune functions. Specifically, we address the role played by the major histocompatibility complex (MHC) antigens as well as adhesion molecules in the initiation of brain immune responses.     

阴道镜下高频电灼术联合α-2a干扰素凝膏治疗尖锐湿疣疗效分析

目的探讨阴道镜下高频电灼术联合重组人干扰素α-2a治疗尖锐湿疣（CA）的效果。方法将165例CA分为3组，A组应用阴道镜下高频电灼术联合重组人干扰素α-2a；B组单纯采用阴道镜下高频电灼治疗；C组应用NS-FII型多功能光谱治疗仪联合肌注重组人干扰素α-2a。结果治疗后3-6个月A、B、C组复发率分别为0％、4．4％、65．4％：半年后人乳头瘤病毒（HPV）转阴率分别为93．5％、85．4％、43．8％，A组明显优于B组，B组明显优于C组，3组比较差异有统计学意义（P〈0．01）。结论阴道镜下高频电灼术联合重组人干扰素α-2a治疗CA可明显降低CA复发率和提高HPV转阴率。     

Interferon (IFN)-α, IFN-γ, interleukin (IL)-2, and arachidonic acid metabolites modulate IL-4-induced IgE synthesis similarly in healthy persons and in atopic dermatitis patients

The role of cytokines and arachidonic acid metabolites in the regulation of IgE production in healthy persons and in atopic dermatitis patients with elevated IgE levels was studied. Interleukin-4 (IL-4) induced IgE production in peripheral blood mononuclear cells (PBMCs) of all donors, and no significant difference was found between the amounts of IgE produced by healthy persons and atopic dermatitis patients. Similarly, recombinant interferon (IFN)-α and IFN-γ, as well as IL-2, inhibited IL-4-induced IgE production to a similar extent in both study groups. To evaluate the role of arachidonic acid (AA) metabolites in the regulation of IgE production, we added indomethacin, an inhibitor of the cyclooxygenase pathway, or nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway, to IL-4-treated cultures. Both indomethacin and NDGA strongly inhibited IL-4-induced IgE production. They also inhibited IL-4-induced IgG4 synthesis. No significant difference in the amount of inhibition was found between the two study groups. We were unable to restore the NDGA-induced inhibition of IgE-production by adding leukotrienes B₄, C₄, D₄, or 5-HETE to the NDGA-treated cultures. PGE₂ also failed to restore the indomethacin-mediated inhibitory effect. Consequently, NDGA- and indomethacin-mediated inhibitory effects do not appear to be mediated by any single factor studied. Collectively, our results show IFNs and IL-2 to be similar in effect in the modulation of IL-4-induced IgE synthesis in healthy and atopic persons. In addition, our results show the importance of AA metabolites in the regulation of IgE and IgG4 synthesis in normal persons as well as in atopic dermatitis patients.     

干扰素a-2b对增生性瘢痕HLA-DR和CD1a分子的影响

目的:探讨干扰素a-2b对增生性瘢痕HLA-DR和CD1α。分子的作用。方法 利用免疫组织化学方法检测6例增生性瘢痕（HS）和6例正常皮肤HLA-DR和CD1α分子的分布及密度,观察干扰素a-2b治疗后HS HLA-DR和CD1α分子的变化。结果:（1）HS组织表皮HLA-DR LC的数量806.67±101.72个//mm2和表皮CD1α LC的数量700.00±108.82个/mm2明显高于正常皮肤510.00±45.07个/mm2,521.24±57.87个/mm（P<0.05）。（2）HS组织HLA-DR分子在角质形成细胞和成纤维细胞中异常出现。（3）于扰素a-2b治疗3d时HS表皮HLA-DR LC及CD1α LC的数量分别为283.34±73.12个/mm2,220.00±83.92个/mm2,7d时516±49.67个/mm2,589.10±108.82个/mm2,干扰素a-2b治疗后HS表皮HLA-DR LC及CD1αLC的数量明显降低（P<0.05）。结论:（1）HLA-DR和CD1α分子数量的增加提示HS和K局部组织可能处于高兔疫应答状态;（2）干扰素a-2b可能通过抑制HLA-DR和CD1α分子降低HS高免疫应答的状态。     

The Leishmania infantum acidic ribosomal protein LiP2a induces a prominent humoral response in vivo and stimulates cell proliferation in vitro and interferon-gamma (IFN-gamma) production by murine splenocytes

The acidic ribosomal proteins of the protozoan parasite Leishmania infantum have been described as prominent antigens during both human and canine visceral leishmaniasis. In this study we present data showing that the intraperitoneal administration in BALB/c mice of the Leishmania LiP2a protein, in the absence of any added adjuvants, elicited a strong humoral response as an indication that the protein is a potent immunogen. Despite the evolutionary conservation of the acidic ribosomal proteins, the antibody response was found to be specific for the Leishmania protein. Another remarkable finding was the observation that the LiP2a protein stimulates the in vitro proliferation of splenocytes from either LiP2a-immunized or naive BALB/c mice. Since similar proliferative indices were observed in T cell-enriched cultures, it is likely that the LiP2a stimulating activity is due mainly to T lymphocyte expansion. Also, the stimulatory effect was demonstrated to be antigen-specific, since the proliferation was abrogated by the presence of anti-LiP2a antibodies. Interestingly, the LiP2a protein stimulated the production of substantial amounts of IFN-gamma in cultured splenocytes from LiP2a-immunized mice. Our data indicate therefore that the immunostimulatory properties shown by this antigen should be taken into account when developing therapeutic and prophylactic vaccines against leishmaniasis.     

Cytokine-induced histamine release from basophils of AIDS patients

Basophil leukocytes obtained from AIDS patients, allergic patients and healthy controls were stimulated in vitro with interleukin 4, lymphotoxin, tumour necrosis factor alpha and interferon gamma to examine the histamine releasing effect. The cytokines caused histamine release from the basophils of approximately half the AIDS patients and from 8-17% of the allergic patients. No response was obtained in the control group. Removal of cell surface immunoglobulins abolished the response to cytokines, indicating an Ig-dependent mechanism. Passive sensitization with cell-derived Ig, with Ig deprived of IgE, or with IgG, indicated that cell-bound IgE was responsible for the cytokine-induced histamine release in AIDS patients. This response may be mediated by cytokine-selective IgE antibodies.     

Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development

1. Download high-res image (259KB)
2. Download full-size image