Correlation between chronic sinusitis subtypes and basophil levels in peripheral blood / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the clinical correlation between peripheral blood basophil levels and chronic sinusitis （CRS） subtypes. Methods:One hundred and twenty-six patients with CRS and 103 healthy cases from physical examination admitted to the First Affiliated Hospital of Soochow University from January 2021 to October 2022 were retrospectively analyzed. According to the histopathological classification, CRS patients were divided into eosinophilic chronic sinusitis （eCRS） group （47 cases） and non eosinophilic chronic sinusitis （non-eCRS） group （79 cases）. The differences among the three groups in peripheral blood inflammation cell counts, eosinophils-to-basophils ratio（bEBR）, basophils-to-neutrophils ratio（BNR）, basophils-to-lymphocytes ratio（BLR）, basophils-to-monocytes ratio（BMR） were compared, and study the correlation between each index and Lund-Mackay score, and the correlation between basophils in peripheral blood and other inflammatory cells. Results:The counts of basophils in the peripheral blood of the healthy control group, eCRS group and non-eCRS group were 0.03±0.01, 0.04±0.02, 0.03±0.02, respectively, the eosinophils-to-basophils ratio（bEBR） were 5.64±4.22, 8.38±5.95, 4.55±3.90, the basophils-to-neutrophils ratio（BNR） were 0.01±0, 0.01±0.01, 0.01±0.01, and the basophils-to-lymphocytes ratio（BLR） were 0.01±0.01, 0.02±0.01, and 0.02±0.01, respectively, the basophils-to-monocytes ratio（BMR） were 0.08±0.04, 0.11±0.06, and 0.08 ±0.04 respectively. There was a statistically significant difference between eCRS group and healthy control group, non-eCRS group（P<0.01）, while there was no statistically significant difference between non-eCRS group and healthy control group（P>0.05）. Basophil counts （r=0.185 5, P<0.05）, BLR（r=0.226 9, P<0.05）, BMR（r=0.228 1, P<0.01） in patients with CRS were positively correlated with Lund Makey score. In addition, basophils were also positively correlated with eosinophils（r=0.479 2, P<0.01）, lymphocytes（r=0.259 4, P<0.01）, and monocytes（r=0.256 4, P<0.01） in patients with CRS. Conclusion:The peripheral blood basophil count, BLR and BMR were significantly increased in eCRS, and were significantly positively correlated with Lund -Makey score. It has the potential to develop into disease biomarkers and new therapeutic targets of eCRS.

Mechanisms of pruritus in bullous pemphigoid / 中华皮肤科杂志

Pruritus is one of the typical clinical manifestations of bullous pemphigoid (BP) . In recent years, researchers have gradually recognized that the histamine-independent itch pathway plays an important role in BP. Eosinophils, basophils, interleukin (IL) -31, IL-4, IL-13, thymic stromal lymphopoietin, periostin and substance P are all closely related to the occurrence of pruritus in BP. This review mainly elaborates research progress in mechanisms related to pruritus in BP.

New insights into roles of basophils in initiating T helper type 2 immunity / 中草药·英文版

Allergic diseases, mainly mediated by T helper type 2 (Th2) immunity, have become a worldwide public health problem. Traditional Chinese medicine (TCM) has long been used in treating and preventing allergic symptoms. As the new target of anti-allergy TCM, basophils, after approximately 140 years since their discovery, are just now gaining respect as important contributors in the pathogenesis underlying allergic inflammation and disease. In addition to their role as effector cells, basophils can release early IL-4, migrate from circulatory system into draining lymph nodes, present antigen to naive CD4+ T cells, and promote the differentiation of Th2 cells. Herein, we briefly summarized the recent research advances of the essential contributions of basophils in the initiation of Th2 immune responses.

Causal Relationship Between Anti-TPO IgE and Chronic Urticaria by In Vitro and In Vivo Tests

PURPOSE: Immunoglobulin (Ig) E autoantibodies against thyroid antigens such as thyroid peroxidase (TPO) have been demonstrated in chronic spontaneous urticaria (CSU) patients in higher frequency than healthy subjects. However, if these IgE autoantibodies can trigger urticaria is still a matter of study. The aim of this study was to investigate the relationship between concomitant IgE autoantibodies against thyroid antigens in CSU. METHODS: Patients with CSU, healthy subjects and patients with autoimmune thyroid disease (ATD) were recruited. Total IgE and specific anti-TPO IgE and IgG were assessed in all subjects. The basophil activation test and skin tests with TPO were performed to demonstrate whether this antigen could selectively induce urticaria reaction in subjects with positive anti-TPO IgE. RESULTS: Anti-TPO IgE was present in all 3 groups (CSU: 34.0%, ATD: 16.6%, healthy subjects: 8.1%). Anti-TPO IgE levels were higher in CSU patients, whereas anti-TPO IgG were higher in ATD patients. After exposure to TPO, CD203c expression from patients with CSU and anti-TPO IgE significantly increased in comparison to the other groups; 33.0% vs. 14.0% in ATD patients and 9.0% in control subjects (P < 0.05). Skin reactions with TPO were higher in patients with CSU according to the intradermal (CSU: 18.0%, ATD: 3.3%, control: 8.0%) and skin prick tests (12.0%, 0%, 0%, respectively). Passive transfer of anti-TPO IgE from a CSU patient to the skin of control subjects without anti-TPO IgE induced a positive skin reaction. CONCLUSIONS: Anti-TPO IgE is not a specific biomarker for CSU. However, IgE against TPO plays a pathogenic role in inducing effector cell activation and skin exacerbation in some patients with CSU.

Allergy to carminic acid: in vitro evidence of involvement of protein-binding hapten

We previously described a rare case of anaphylaxis presumably induced by carminic acid in cochineal dye used as a food additive. In this study, highly pure carminic acid was added to an albumin-containing buffer at various concentrations, followed by serial dilution. Varying the mixing ratio of carminic acid and albumin affected the extent of histamine release from passively sensitized basophils. Similar basophil histamine release occurred with carminic acid-globulin solutions. These results provide experimental evidence indicating that basophil activation is dependent on hapten (carminic acid) and carrier (protein) interaction.

Dimerized, Not Monomeric, Translationally Controlled Tumor Protein Induces Basophil Activation and Mast Cell Degranulation in Chronic Urticaria

Translationally controlled tumor protein (TCTP) is also known as histamine releasing factor as it has the ability to activate mast cells. To investigate the role of TCTP in the pathogenesis of chronic spontaneous urticaria (CSU), we evaluated serum level of TCTP and effect of TCTP on basophil and mast cell degranulation. TCTP levels in the sera from 116 CSU patients and 70 normal healthy controls (NCs) were measured by ELISA. CD203c expression on basophils from CSU patients and β-hexosaminidase release from Laboratory of Allergic Disease 2 mast cells were measured upon stimulation monomeric and dimeric TCTP. Non-reducing Western blot analysis was used for detecting dimeric TCTP. No difference was observed in serum TCTP levels between CSU patients and NCs (p=0.676). However, dimeric TCTP intensity on Western blot was stronger in CSU patients than in NCs. TCTP levels were higher in patients with severe CSU (p=0.049) and with IgG positivity to FcɛRIα (p=0.038). A significant positive correlation was observed between TCTP and eosinophil cationic protein levels (Spearman's rho=0.341; p=0.001). Both basophil and mast cell degranulation were significantly increased after stimulation with dimeric TCTP, but not with monomic TCTP. The ability of TCTP to activate basophil and mast cells is dependent on dimerization, suggesting that the inhibition of TCTP dimerization can be a therapeutic option for CSU. Association between TCTP levels and the presence of IgG to high affinity Fc epsilon receptor I alpha subunit in CSU patients indicates that autoimmune mechanisms may be involved in the dimerization of TCTP.

Prueba de activación de basófilos: aspectos técnicos, metodológicos y su utilidad clínica / Basophil activation test: technical aspects, methodology and clinical utility

Resumen Introducción. La prueba de activación de basófilos (PAB) se considera una técnica confiable y segura para el diagnóstico de problemas alérgicos. Objetivo. Profundizar en el estado del arte de la PAB y su utilidad clínica. Materiales y métodos. Se realizó una revisión narrativa de la literatura mediante la búsqueda electrónica en las bases de datos y metabuscadores Ovid Medline, Google Scholar y PubMed, sin limitar la búsqueda por fecha, idioma o tipo de artículo. Se buscaron artículos sobre los detalles técnicos de la PAB y su utilidad clínica en el manejo de las enfermedades alérgicas. Resultados. De los marcadores de activación, CD63 ha sido el más estudiado y es el que mejor representa un evento de degranulación anafiláctica, mientras que CD203c es representativo de varias formas de degranulación. La superioridad de uno sobre otro como prueba diagnóstica depende del problema alérgico estudiado. En cuanto a los métodos de detección de basófilos, su selección con un único marcador, CCR3, se propone como una opción con buena relación de costo-efectividad. Conclusiones. La PAB es una herramienta prometedora para evaluar en clínica las reacciones alérgicas de forma segura. Es necesario una mayor estandarización de protocolos para obtener resultados más reproducibles.

Abstract Introduction: Basophil activation test (BAT) is considered a reliable and safe technique for diagnosing allergic diseases. Objective: To make a thorough analysis of the state of the art regarding BAT and its clinical utility. Materials and methods: A narrative literature review of BAT and its clinical utility in the management of allergic diseases was performed in the Ovid Medline, Google Scholar and PubMed databases and metasearch engines, without limiting the search by date, language or type of article. Results: Regarding basophil activation markers, CD63 is the most studied and the best representative of anaphylactic degranulation, while CD203c is representative of several types of degranulation. The superiority of one activation marker over the other as a diagnostic tool depends on the allergic disease under study. With respect to basophil detection methods, selection with a single marker, CCR3, is proposed as an option with a good cost-effectiveness ratio. Conclusions: BAT is a promising tool to evaluate clinically allergic reactions in a safe manner. Better standardization of protocols is necessary to achieve reproducible results.

Basophils are increased and express increased levels of interleukin-4 in the parotid lesions of Kimura disease

BACKGROUND: Kimura disease (KD) is a systemic soft-tissue disease that leads to formation of painless masses in lymph nodes, with the highest predilection for the head and neck and especially the parotid gland. KD lesions are characterized by marked eosinophil infiltration, production of IgE and increased expression of T-helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, etc.). Skewing to a Th2 inflammation is also demonstrated in the peripheral blood, with elevated eosinophils and high IgE levels. It is thought that basophils may play important roles in orchestrating this Th2 inflammation via IL-4 production leading to the induction of IgE synthesis as well as eosinophil infiltration. However, there are no reports as yet on the role of basophils in KD. OBJECTIVE: The present study was performed to investigate the potential role of basophils in the pathogenesis of KD. In this context we also examined the expression of IL-4 in basophils in the KD lesions. METHODS: By immunohistochemistry using a monoclonal antibody against a basophil marker ProMBP1 we investigated the number and distribution of basophils in the KD lesions. By double immunohistochemistry we analyzed the colocalization of IL-4 in basophils. RESULTS: There was an increased number of basophils infiltrating the KD parotid gland lesions as compared to that in normal control parotid tissue. By double-immunofluorescence we found that approximately 7% of IL-4-positive cells in KD patients' parotid glands were basophils. CONCLUSION: Basophils may also play a role in the pathogenesis of KD, leading to the induction of IgE synthesis and eosinophil infiltration.

Detection of thyroid autoantibodies in patients with chronic urticaria and analysis of clinical features / 中华皮肤科杂志

Objective To investigate clinical and serological characteristics of thyroid autoantibody-positive patients with chronic urticaria.Methods A total of 70 inpatients with chronic urticaria were enrolled from the Department of Dermatology of Hangzhou Third Hospital between January and December in 2016,and divided into 2 groups according to the presence or absence of thyroid autoantibodies.Clinical manifestations,autologous serum skin test (ASST)results,hospital days,discharge outcome,routine blood test results,antibodies,and total serum IgE and IgG levels were compared between the 2 groups.Results Of 70 patients with chronic urticaria,26 (37.1％) had positive thyroid autoantibodies,while 44 (62.9％) had negative thyroid autoantibodies.Compared with patients with negative thyroid autoantibodies,patients with positive thyroid autoantibodies showed significantly larger wheals and more severe itching (z =4.399,P ＜ 0.001),longer duration (z =4.43,P ＜ 0.001) and higher frequency of clinical symptoms (z =7.362,P ＜ 0.001),higher risk of being complicated by systemic symptoms (x2 =7.068,P ＜ 0.05),higher positive rates of ASST (x2 =6.559,P ＜ 0.05),longer hospital stay (t =3.184,P ＜ 0.05),lower cure rate at discharge (x2 =5.524,P ＜ 0.05) and less number of basophilic granulocytes (t =3.19,P ＞ 0.05).Conclusion Chronic urticaria patients with positive thyroid autoantibodies show more severe urticarial condition,and are commonly complicated by positive ASST and decreased levels of basophilic granulocytes.

Detection of thyroid autoantibodies in patients with chronic urticaria and analysis of clinical features / 中华皮肤科杂志

Objective To investigate clinical and serological characteristics of thyroid autoantibody-positive patients with chronic urticaria.Methods A total of 70 inpatients with chronic urticaria were enrolled from the Department of Dermatology of Hangzhou Third Hospital between January and December in 2016,and divided into 2 groups according to the presence or absence of thyroid autoantibodies.Clinical manifestations,autologous serum skin test (ASST)results,hospital days,discharge outcome,routine blood test results,antibodies,and total serum IgE and IgG levels were compared between the 2 groups.Results Of 70 patients with chronic urticaria,26 (37.1％) had positive thyroid autoantibodies,while 44 (62.9％) had negative thyroid autoantibodies.Compared with patients with negative thyroid autoantibodies,patients with positive thyroid autoantibodies showed significantly larger wheals and more severe itching (z =4.399,P ＜ 0.001),longer duration (z =4.43,P ＜ 0.001) and higher frequency of clinical symptoms (z =7.362,P ＜ 0.001),higher risk of being complicated by systemic symptoms (x2 =7.068,P ＜ 0.05),higher positive rates of ASST (x2 =6.559,P ＜ 0.05),longer hospital stay (t =3.184,P ＜ 0.05),lower cure rate at discharge (x2 =5.524,P ＜ 0.05) and less number of basophilic granulocytes (t =3.19,P ＞ 0.05).Conclusion Chronic urticaria patients with positive thyroid autoantibodies show more severe urticarial condition,and are commonly complicated by positive ASST and decreased levels of basophilic granulocytes.

Las grandes directrices de la investigación en homeopatía (parte 1 de 2) / The broad guidelines of research in homeopathy (part 1 of 2)

La Homeopatía se fundó sobre un método que es, al mismo tiempo, experimental y empírico. La Homeopatía es parcialmente experimental debido a que su semiología nació con la experimentación sobre el hombre sano, efectuada según el método hahnemanniano; asimismo, es parcialmente empírica porque se basa en el trabajo de observación de los médicos homeópatas y en la adquisición de la experiencia práctica, la cual ha sido transmitida a alumnos deseosos de utilizar este método terapéutico. La investigación en Homeopatía se ha desarrollado progresivamente, tratando de integrar las aportaciones de estos dos métodos: experimental y empírico. De hecho, los esfuerzos realizados por situar a la Homeopatía dentro de una metodología rigurosa se remontan al inicio mismo de esta disciplina, inscrita desde su origen por Hahnemann dentro de la línea científica y médica original...

Homeopathy is in part experimental because the semiology was born with the experimentation on the healthy man, which was performed according to Hahnemann´s method; it is also partly empirical because much work is based on the observation of homeopaths and the acquisition of practical experience, which has been transmitted to students eager to use this therapeutic method. Research in Homeopathy has been gradually developed, trying to integrate the contributions of these two methods: experimental and empirical. In fact, efforts have been made to place homeopathy within a rigorous methodology dating back to the beginning of the discipline itself, from its origin registered by Hahnemann within the original scientific and medical field...

Chlorpheniramine-induced anaphylaxis diagnosed by basophil activation test

Chlorpheniramine is a widely prescribed H1-antihistamine for relieving urticaria or histamine-mediated allergic reactions. However, although rare, it may cause immediate hypersensitivity reactions. The diagnosis is usually made by provocation test, but its application is often limited due to comorbidities or potential risk of severe reactions. In those cases, skin tests and basophil activation tests can be considered as additional diagnostic tests for the drug allergy. Here, we report a 33-year-old female with underlying chronic urticaria, who recurrently developed anaphylaxis after chlorpheniramine administration. Intradermal test showed positive responses in the patient at 0.02 mg/mL of chlorpheniramine, but not in healthy controls. Basophil activation test showed significant up-regulation of CD63 and CD203c by chlorpheniramine. The present case reminds the rare but potential allergic risk of chlorpheniramine, and also suggests the potential utility of basophil activation test in making the diagnosis.

Role of basophils in the imbalance of Th1/Th2 response in collagen-induced arthritis in mice / 中国比较医学杂志

Objective To investigate the role of basophils in the imbalance of Th 1/Th2 response in mouse models of collagen-induced arthritis(CIA).Methods 4-6-weeks old C57/BL6 mice were immunized with collagen at multiple points on the back and foot twice (0 and 3 weeks) to establish a mouse model of collagen-induced arthritis.Blood samples were collected before the first immunization and 1, 3, 6 and 9 weeks after immunization , and cells from lymph nodes were collected.Flow cytometry and ELISA were employed to detect the levels of basophils and IL-4, and the joint swelling was scored.Results Mouse model of CIA was successful established .The ratio of IL-4/IFN-γof the CIA group was significantly lower than that in the mice before CIA modeling and the control group , indicating a Th2-dominant response .At the same time, the peripheral basophils counting and percentage of IL-4 positive basophils of the CIA group were significantly higher than those of the control group .While, the IL-4/IFN-γratio of the CIA group was significantly higher than that of the control group , indicating a Th1-dominant response .The peripheral basophils counting of the CIA group was slightly lower than that of the control group .Conclusion Basophils may participate in the development of CIA in mouse models through affecting the imbalance of Th 1/Th2 response.

Oral allergy syndrome caused by crown daisy and sesame leaf

Oral allergy syndrome (OAS) is a subtype of food allergy composing of itching sense and edema in the oral cavity, lips, throat, pharynx, and larynx following ingestion of some fresh fruits or vegetables. Although the major pathogenic mechanism of OAS is known to be IgE-mediated response, here we experienced a case of OAS due to crown daisy (CD) and sesame leaf (SL) mediated by a non-IgE antibody mediated mechanism. A 33-year-old female visited our clinic to evaluate numbness of the tongue and gingiva after eating fresh CD and SL for 2 years. The patient had suffered from allergic rhinitis and atopic dermatitis for 20 years and took medications intermittently. There had been a history of food allergy to crab and shrimp. The serum total IgE level was elevated (404 kU/mL). The skin prick test showed strong positive reactions to tree and weed pollens, but not to CD and SL extracts. Enzyme-linked immunosorbant assay for detecting serum specific IgE to crude extracts of CD and SL showed negative results. The basophil activation test performed with crude extracts of CD or SL showed significant up-regulation of CD63-positive basophils by both CD and SL. In conclusion, we report a case of OAS due to CD and SL, not associated with pollen allergy, which is shown to be mediated by a non-IgE mediated mechanism.

Low Basophil Count and Red Cell Distribution Width at Birth May Predict the Development of Neonatal Necrotizing Enterocolitis: A Matched Control Study

OBJECTIVE: The pathophysiology of necrotizing enterocolitis (NEC) is incompletely understood. There were some reports that the pathogenesis of NEC involves intrauterine process and infants with fulminant NEC had low lymphocyte count. Thus, we investigated complete blood count (CBC) parameters of infants at birth and their mothers near delivery. METHODS: We retrospectively reviewed the medical records of NEC patients and controls. The CBC parameters were compared between infants with NEC (modified Bell's criteria stage > or =Ia, n=82) and controls matched for gestational age, birth weight, gender, and race (n=169). The blood test findings were obtained from infants within the first 2 hours of life and from mothers as the latest one before delivery. RESULTS: Statistically different findings at birth were found in NEC infants; red cell distribution width (RDW) and basophil count. In the multiple logistic regression analysis after adjustment for gestational age, birth weight, and gender, several infantile independent risk factors were identified; basophil count <40/microL (odds ratio [OR], 4.60; 95% confidence interval [CI], 2.18 to 9.73; P<0.001) and low RDW (OR, 7.15; 95% CI, 2.93 to 17.41; P<0.001). CONCLUSION: We found that NEC was associated with low infantile RDW and basophil count at birth. These findings might support roles of red blood cell and basophil in the pathogenesis of NEC, which might predict development of NEC with neonatal findings at birth.

Threshold for Positivity and Optimal Dipyrone Concentration in Flow Cytometry-Assisted Basophil Activation Test

PURPOSE: Basophil activation occurs both in patients with immediate hypersensitivity reactions to anti-inflammatory drugs and in healthy controls in a dose-dependent manner. Our aims were to define the optimal basophil activation test (BAT) concentration and the threshold for BAT positivity for dipyrone. METHODS: From 45 patients with a positive history of an immediate hypersensitivity reaction to dipyrone, we found 20 patients with dipyrone-induced anaphylaxis demonstrating positive skin tests. All selected patients, as well as 10 healthy controls, were tested in vivo and in vitro. BAT was performed using Flow 2CAST technique with three low dipyrone concentrations: 25 microg/mL (c1), 2.5 microg/mL (c2) and 0.25 microg/mL (c3). The threshold for BAT positivity was established using receiver operating characteristics (ROC) curve analysis. RESULTS: Using ROC curve analysis the highest area under curve, 0.79 (0.63-0.95) (P<0.01), was found for c3. When the highest stimulation indexes from the three concentrations for each patient were used, ROC curve analysis revealed an area under curve of 0.81 (0.65-0.96) (P<0.01), sensitivity and specificity were 0.70 and 1 and the optimal threshold value for BAT positivity was 1.71. Thirteen patients had a positive BAT for at least one of the tested dipyrone concentrations. All healthy controls presented negative BAT. CONCLUSIONS: BAT might be a useful technique to diagnose dipyrone allergy, provided all three low dipyrone concentrations are used together. With an assay-specific threshold of 1.71, ROC curve analysis yields 70% sensitivity and 100% specificity.

Threshold for Positivity and Optimal Dipyrone Concentration in Flow Cytometry-Assisted Basophil Activation Test

PURPOSE: Basophil activation occurs both in patients with immediate hypersensitivity reactions to anti-inflammatory drugs and in healthy controls in a dose-dependent manner. Our aims were to define the optimal basophil activation test (BAT) concentration and the threshold for BAT positivity for dipyrone. METHODS: From 45 patients with a positive history of an immediate hypersensitivity reaction to dipyrone, we found 20 patients with dipyrone-induced anaphylaxis demonstrating positive skin tests. All selected patients, as well as 10 healthy controls, were tested in vivo and in vitro. BAT was performed using Flow 2CAST technique with three low dipyrone concentrations: 25 microg/mL (c1), 2.5 microg/mL (c2) and 0.25 microg/mL (c3). The threshold for BAT positivity was established using receiver operating characteristics (ROC) curve analysis. RESULTS: Using ROC curve analysis the highest area under curve, 0.79 (0.63-0.95) (P<0.01), was found for c3. When the highest stimulation indexes from the three concentrations for each patient were used, ROC curve analysis revealed an area under curve of 0.81 (0.65-0.96) (P<0.01), sensitivity and specificity were 0.70 and 1 and the optimal threshold value for BAT positivity was 1.71. Thirteen patients had a positive BAT for at least one of the tested dipyrone concentrations. All healthy controls presented negative BAT. CONCLUSIONS: BAT might be a useful technique to diagnose dipyrone allergy, provided all three low dipyrone concentrations are used together. With an assay-specific threshold of 1.71, ROC curve analysis yields 70% sensitivity and 100% specificity.

Recent applications of basophil activation tests in the diagnosis of drug hypersensitivity

Immediate-type drug hypersensitivity is an increasingly significant clinical issue; however, the diagnosis is frequently hindered due to lack of safe and precise diagnostic tests. Flow cytometry-assisted basophil activation test is a safe in vitro diagnostic tool for assessing basophil activation upon allergen stimulation. In this review, we have summarized current literature on the diagnostic utilities, new indications, and methodological aspects of the basophil activation test for the diagnosis of drug hypersensitivity.

IL-4 Derived from Non-T Cells Induces Basophil- and IL-3-independent Th2 Immune Responses

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

Murine basophils express highly in liver and regulate priming of na(i)ve CD4+ T cells to develop into Th2 cells / 中华微生物学和免疫学杂志

Objective To compare the levels of murine basophils distribution in different organs and analyze the characteristics of CD4+T cells activation/differentiation regulated by basophils.Methods Firstly,the mononuclear leukocytes were isolated separately from periphery blood,liver,spleen,lung and lymph nodes and the percentages of FcεR I+CD49b+ basophils in different organs were investigated.Secondly,liver basophils were purified by immuno-microbead strategy and co-clutured with different cytokines for 24 h.Apoptosis status of basophils was detected by Annexin V straining method.Thirdly,Mice were subcutaneously implanted with a miniosmotic pump containing 5 μg IL-3.At day 7 after implantation,liver mononuclear cells were harvested and the percentages of basophils were analyzed.Finally,Th1/Th2 polarization influenced by basophils orientated cytokines was investigated when naive OT-Ⅱ CD4 T cells were stimulated with spleen dentritic cells and OVA peptides.Results The percentage of murine basophils in mononuclear leukocytes of liver was significantly higher than that of periphery blood,spleen,lung and lymph nodes under physiological condition.Both of in vitro and ex vivo experiments showed that IL-3 played an inhibitory role on apoptosis of basophils.Cytokines secreted by basophils was investigated to induce Th2 polarization and inhibit Th1 response when naive OT-Ⅱ CD4 T cells were co-cultured with spleen dentritic cells and OVA peptides.Conclusion Th2 response was enhanced and Th1 response was down-regulated by murine basophils,which implied that basophils might participate in the construction of liver specific physiological immuno-tolerant microenvironment.