Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.     

TIL／rIL－2免疫过继疗法治疗晚期瘤性胸水初探

７例晚期瘤性胸水的肿瘤浸润淋巴细胞（ＴＩＬ）经体外诱导培养３～１２ｄ，扩增１～９倍．其ＣＤ８及ＩＬ－２Ｒ阳性细胞百分率增加２．４３和２．７６倍；ＮＫ活力增加３．２９倍，与培养前后比较有显著差异。ＴＩＬ／ｒＩＬ－２（重组人白细胞介素２）胸腔内回输后，４例胸水及胸水中肿瘤细胞消失，癌胚抗原（ＣＥＡ）回至正常水平，２例胸水减少，１例因多房性胸水停止治疗，ＣＥＡ水平上升。经１～８个月随访患者心、肝、肾功能正常。     

Intranasal treatment with ovalbumin but not the major T cell epitope ovalbumin 323–339 generates interleukin-10 secreting T cells and results in the induction of allergen systemic tolerance

BACKGROUND: Nasal administration of major peptide T cell epitopes gives contradictory data on the induction of peripheral tolerance. OBJECTIVE: To compare the prophylactic effect of intranasal treatment (INT) on the development of an allergic response, using either ovalbumin (OVA) or its major T cell epitope OVA 323-339 (OVAp). METHODS: BALB/c mice were treated intranasally with OVA or OVAp and subsequently immunized s.c. with OVA. Anti-OVA-specific antibody, T cell proliferation and cytokine responses were analysed. In an adoptive transfer model using OVAp specific TCR transgenic (Tg) T cells from D011.10 mice, in vivo tracking and characterization of transferred T cells in the cervical, inguinal and bronchial lymph nodes (BLN) and in the spleen were determined by FACS analysis. RESULTS: Prophylactic INT with OVA induced T cell tolerance towards subsequent OVA s.c. immunizations, inhibiting OVA specific T cell proliferation, IgE and IgG1 production, in contrast to INT with OVAp, which was unable to induce tolerance. In vivo analysis of transferred OVA-specific TCR Tg T cells showed that INT with OVA induced a preferential activation of T cells in BLN, as opposed to a broad, systemic activation with OVAp. In vivo, OVAp INT led to faster and more sustained cell division cycles than OVA INT. Ex vivo, tolerance to OVA was associated with the generation of IL-10 secreting CD4(+) T cells in BLN of OVA-treated mice only. CONCLUSION: INT with OVA but not with OVAp led to regional (as opposed to systemic) T cell activation and the induction of IL-10 secreting CD4(+) T cells in BLN, potentially critical steps in the induction of T cell-specific tolerance via the nasal route.     

军人花粉症106例快速免疫治疗

目的　探讨军人花粉症治疗的有效方法。方法　采用提高起始浓度和快速递增浓度 ,上臂外侧皮下注射的方法对 10 6位军人花粉症患者行快速免疫治疗 ,并对每一位患者治疗前后检测血清中总IgE和嗜酸细胞阳离子蛋白 (ECP)。 结果　治疗前后患者总IgE和ECP值有显著性差异。 10 6例患者经 1～ 3年随访复查 ,78例 2个以上发病季节未发作 ,或仅有轻微鼻痒、眼痒 ,18例症状减轻 ,发病时间缩短半月 ,10例症状无明显改善。显效 82例 ,有效 14例 ,无效 10例 ,总有效率为 90 .5 7%。结论　快速免疫治疗能使患者血清总IgE和ECP下降 ,对军人花粉症疗效好。     

Dendritic cells therapy

Dendritic cells (DC) are potent regulators of the immune system. Today, much research is being done trying to understand how DCs can be harnessed to induce immunity and how we can better exploit their potentials. Here, the present understanding of DC biology, function and use is summarized.     

Recombinant allergen fragments as candidate preparations for allergen immunotherapy

Background: Lately, renewed interest has arisen in the new forms of allergen immunotherapy because they may offer alternatives for drug treatment. Objective: The purpose of this study was to develop a well-characterized preparation of the main respiratory cow dander allergen, Bos d 2, with attenuated allergenic activity. Methods: The immunologic characteristics of Bos d 2 preparations were studied by indirect IgE ELISA, ELISA inhibition, Western blotting, histamine release, skin prick tests, and the proliferation tests of allergen-specific T-cell clones. Results: The complete recombinant Bos d 2 was observed to bind effectively, IgE of cow-allergic patients in indirect ELISA. In other experiments, the IgE-binding capacity of recombinant Bos d 2 proved to be lower compared with native Bos d 2. When the two overlapping recombinant fragments of Bos d 2 (corresponding amino acids 1-131 and 81-172, respectively) covering the whole molecule were compared with the complete recombinant Bos d 2 with several methods, only a low level of residual reactivity was observed. For example, recombinant fragments could not bind antibody at all in ELISA inhibition tests retaining, however, some reactivity in skin prick tests. In contrast, the fragments were able to stimulate vigorously Bos d 2-specific T-cell clones. Conclusion: The approach we have taken may offer a simple and reproducible way to produce hypoallergenic preparations for immunotherapy, circumventing simultaneously some of the problems of other experimental methods such as individual T-cell epitope recognition in peptide-based immunotherapy. (J Allergy Clin Immunol 1997;100:721-7.)     

Immunotherapy vs inhaled budesonide in bronchial asthma: an open, parallel, comparative trial

Background Budesonide, an inhaled corticosteroid and specific immunotherapy, are both routinely used in the treatment of bronchial asthma. However, there are as yet, no studies comparing the effects of budesonide vs immunotherapy. Objective The aim of this study is to compare the effects of budesonide with immunotherapy in patients having perennial asthma. Methods This study is an open, parallel, comparative trial, in which 51 young patients were administered either immunotherapy or budesonide for 1 year and their global symptom scores and FEV₁, values assessed. Both treatments were abruptly discontinued after 12 months and the effects of cessation analysed. Results The use of budesonide resulted in a faster and more striking improvement during the first few months as compared to immunotherapy, with an even more rapid decline in benefits on cessation of budesonide. Immunotherapy on the other hand, resulted in slow but steady improvement which did not decline as rapidly as budesonide on cessation. Conclusion Although this was an open trial, it could be concluded that relief with inhaled corticosteroids in bronchial asthma is more rapid than immunotherapy; however the decline in benefit on cessation of inhaled cortieosteroid is even more rapid, a phenomenon not seen with immunotherapy.     

Humanized anti-CD4 monoclonal antibody therapy of autoimmune and inflammatory disease

We have investigated the biological and therapeutic properties of a humanized anti-CD4 MoAb, hlgGl-CD4, in patients with refractory psoriasis and rheumatoid arthritis (RA). hIgGl-CD4 is a modulating, non-depleting MoAb, which induced a first-dose reaction in most patients treated. It provided brief symptomatic relief in both conditions, and psoriasis appeared easier to control with conventional agents after MoAb therapy. At the doses used, hIgGl-CD4 did not synergize therapeutically with the pan-lymphocyte MoAb CAMPATH-1H (C1H) in patients with RA treated sequentially with both agents. There were no serious adverse effects definitely attributable to therapy. Our results are compared with those of other CD4 MoAb studies, and factors influencing the outcome of therapy are discussed.     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.     

Identification of a naturally processed cyclin D1 T-helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry

T-helper (Th) cells play an important role in orchestrating the effector function of CTL in anti-tumor immunity. However, only a limited number of Th cell epitopes has been characterized. Here we describe a novel approach for identifying naturally processed and presented peptides derived from chosen antigens. This method combines a transfection step of antigen-presenting cells with a vector encoding a fusion protein between the Ii chain and the antigen of interest, elution of the HLA-bound peptides and identification of the antigen-derived peptides by mass spectrometric comparison to the non-transfected cells. In vitro-stimulated Th cells against the identified peptide of interest specifically recognize transfectants overexpressing the cognate antigen. Using this approach, we were able to identify the HLA-DR4-restricted Th cell epitope NPPSMVAAGSVVAAV derived from cyclin D1, which is frequently overexpressed in tumors. This method will help in identifying peptide candidates for vaccination studies for tumor immunotherapy.