[Investigation on cognition, diagnosis and treatment status of chest tightness variant asthma among Chinese pediatricians].

Objective: To evaluate the awareness, diagnosis and treatment of chest tightness variant asthma (CTVA) among pediatricians in China. Methods: The survey was conducted by convenient sampling method. Pediatricians with professional title of attending physician and above from different grades hospitals in 30 provinces were invited to conduct online questionnaire surveys through WeChat, pediatricians scan QR codes to complete electronic questionnaires in the mini program from January 16th to February 4th, 2021. The contents of questionnaire included the awareness, diagnosis and treatment of CTVA, and comparing the differences between pediatricians in secondary hospitals and tertiary hospitals. Results: A total of 1 529 pediatricians participated in the survey, and 1 484 (97.06%) pediatricians completed the questionnaire and included in the analysis, including 420 males (28.30%). The awareness rate of CTVA among pediatricians was 77.83 % (1 155/1 484). Pediatricians in tertiary hospitals had higher rates of awareness of CTVA than pediatricians in secondary hospitals [81.86% (898/1 097) vs 66.41% (257/387), P<0.001] and had better execution of the guidelines [89.15% (978/1 097) vs 79.59% (308/387), P<0.001]. A total of 93.06 % (1 381/1 484) of pediatricians' first-line treatment included inhaled corticosteroids (ICS) for CTVA. Among them, a higher proportion of pediatricians in tertiary hospitals used ICS included regimens for first-line treatment of CTVA compared with pediatricians in secondary hospitals [94.90% (1 041/1 097) vs 87.86% (340/387), P<0.001]. The reported well control rate of CTVA was 32.08% (476/1 484), which was significantly lower in secondary hospitals than that in tertiary hospitals [17.31% (67/387) vs 37.28% (409/1 097), P<0.001]. Conclusion: Most pediatricians are well aware of CTVA, among which there is a certain gap in clinical practice between pediatricians in secondary hospitals and tertiary hospitals in terms of understanding, diagnosis, and treatment of CTVA.

[Review and perspective of clinical research involving chest tightness variant asthma in China].

Chest tightness variant asthma (CTVA) was first reported and named by Chinese scholars in 2013. It is a new clinical type of asthma characterized by chest tightness as the only or primary symptom, without typical asthma manifestations such as recurrent wheezing and shortness of breath, and without wheezing sounds heard during lung auscultation. The overall epidemiological data on CTVA is currently unavailable. Its pathogenesis is similar to that of typical asthma, involving eosinophilic airway inflammation. Due to the lack of typical clinical manifestations, insufficient knowledge of this disease in some clinicians and some other reasons, CTVA is susceptible to misdiagnosis or missed diagnosis. Currently, the diagnostic criteria for CTVA are: chest tightness as the only or primary symptom, without typical asthma symptoms and signs such as wheezing and shortness of breath, and with any one of the objective indicators of variable airflow limitation. Effective anti-asthma treatment is required, and other diseases that cause chest tightness, such as cardiovascular, digestive, nervous, muscular, and mental diseases should be excluded. CTVA treatment follows that of typical asthma, but the specific treatment duration is uncertain and may require long-term management. Traditional Chinese medicine has shown some therapeutic effects on CTVA. Most CTVA patients have a good prognosis after active anti-asthma treatment. This paper analyzes and summarizes the research of CTVA in China from 2013 and provides new perspectives for further exploration of CTVA.

[Annual progress in treatment of bronchial asthma 2022].

Bronchial asthma is one of the most common chronic inflammatory airway diseases. Its incidence is increasing annually worldwide, posing a heavy medical burden to society and individuals. At the same time, continuous improvement has been made in the diagnosis and treatment strategies of asthma. With the advancement of basic research and the emergence of evidence-based evidence on asthma, new drugs, updated ideas and strategies have appeared in the field of asthma treatment. This article reviewed the progress and achievements in the field of asthma treatment from 1st October 2021 to 30th September 2022, as well as several updated guidelines and consensus guidance on asthma, providing clinical perspective for the treatment of asthma.

[Expression and significance of Nek2B and ß-catenin in triple negative breast cancer].

Objective: To investigate the expression and significance of Nek2B and ß-catenin expression in triple negative breast cancer (TNBC) at molecule levels. Methods: By using the methods of bioinformatics [GEO2R online tool, gene ontology (GO) function analysis, KEGG biological pathway enrichment analysis], the differentially expressed genes were screened from TNBC microarray data.Expression levels of Nek2B and ß-catenin TNBC cell lines were detected by Western blot and qRT-PCR.From January 1, 2007 to December 31, 2012, eighty cases of TNBC were collected from the Second Hospital of Shanxi Medical University. The expression of Nek2B in TNBC tumor tissue was detected by immunohistochemistry and tissue microarray, and the relationship between Nek2B and clinical pathological characteristics of TNBC was analyzed. Results: Through bioinformatics analysis of the cDNA chip sets of 2 TNBC tumors(GSE38959,GSE27447), 998 differentially expressed genes were obtained in the initial screening, and 13 differentially expressed genes were revealed after intersection. The results of biological pathway analysis showed that the common differential expression genes were closely related to Wnt/ß-catenin pathway, among which Nek2 expression showed the greatest difference and was associated with poor prognosis. Expression intensity of Nek2B and repeated ß-catenin in the same TNBC cell line was consistent.The results of immunohistochemistry showed that the high expression of Nek2B was related to the high histological stage (G3;84.3% vs.37.9%, P<0.001), lymph node metastasis group (76.7% vs.54.1%, P=0.032), high Ki-67 positive index group (78.6% vs.52.6%, P=0.007) and ß-catenin positive expression group (72.5% vs.27.3%, P=0.018). Conclusions: The high level of Nek2B expression is related to a poor prognosis in TNBC patients. In TNBC tissues and cells, the expression of Nek2B is correlated with ß-catenin, suggesting that Nek2B may affect the occurrence and development of TNBC by regulating the Wnt/ß-catenin patients signaling pathway.

Global public interest in systemic lupus erythematosus: an investigation based on internet search data.

OBJECTIVE: This study aims at investigating the global public interest in seeking information about systemic lupus erythematosus (SLE) using Google Trends (GT). METHODS: An electronic search was performed using GT with the search term lupus as well as the option of disease from January 2004 to December 2018. Cosinor analysis was applied to detect the seasonality of SLE-related relative search volume (RSV). In addition, analysis on SLE-related topics including "hot topics" and "top rising topics" was also conducted. RESULTS: Overall, SLE-related RSV showed a decreasing trend from January 2004 to December 2013 and then demonstrated a slowly increasing trend from January 2014 to December 2018. Cosinor test showed no significant seasonal variation in SLE-related RSV (p > .025). RSV peaked in May and reached the trough in November. The top seven rising topics were Selena Gomez, Sjögren syndrome, autoimmunity, rheumatoid arthritis, rheumatology, antinuclear antibody and autoimmune disease. CONCLUSION: The results from GT analysis showed slowly increasing internet searches for SLE in recent years. This trend was followed by a peak of RSV in May and reached its lowest level in November. However, globally, the results did not reveal a significant seasonal variation in GT for SLE. Additionally, the top fast-growing topics regarding SLE may be valuable for doctors and nurses to provide timely education of the disease to patients, as well as promote the development of public health.

[Efficacy of nasal CPAP and aerobic exercise of different intensity in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes mellitus].

Objective: To explore the therapeutic efficacy of nasal Continuous Positive Airway Pressure (CPAP) and aerobic exercise of different intensity in patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) and Type 2 Diabetes Mellitus (T2DM). Methods: A total of 112 patients with OSAHS and T2DM, including 53 males and 59 females, with a mean age of (66.9±7.8) years old, from the Fourth Rehabilitation Hospital of Shanghai and the Second Affiliated Hospital of Soochow University from January 2017 to December 2018 were enrolled prospectively. There were divided into two groups based on whether received nasal CPAP therapy: 50 cases in nasal CPAP+aerobic exercise group and 62 cases in aerobic exercise group. Subsequently, patients in nasal CPAP+aerobic exercise group were randomly divided into two subgroups: moderate and low intensity aerobic exercise (26 and 24 cases respectively). All patients completed nasal CPAP and (or) aerobic exercise of different intensity for 20 weeks. The therapeutic efficacy of polysomnography (PSG) parameters, glycolipid metabolism, 6 minutes walking distance (6 MWD), and rate of perceived exertion (RPE) were compared between each group before and after treatment. Results: Pre-and post-intervention, PSG parameters, body mass index (BMI) [(26.6±3.7) vs (24.3±2.8) kg/m(2)], RPE [(16.4±1.3) vs (12.2±2.6) score], 6 MWD [(372.6±59.7) vs (441.5±75.6) m] and glucolipid metabolism indexes were improved significantly in nasal CPAP+aerobic exercise group (all P<0.05), such as fasting blood glucose [(7.4±2.4) vs (6.2±1.6) mmol/L], glycosylated hemoglobin [(7.6±1.2)% vs (6.6±0.7)%], fasting insulin [(10.8±4.4) vs (6.9±3.4) µU/L], insulin resistance index [(3.5±1.9) vs (1.9±1.2)], total cholesterol [(4.0±0.9) vs (3.5±0.9) mmol/L], low density lipoprotein cholesterol [(4.2±0.6) vs (3.1±0.8) mmol/L]; BMI, exercise endurance, some glucolipid metabolism indexes and PSG parameters were also improved in aerobic exercise group (P<0.05). After 20 weeks' intervention, it showed statistically significant differences in PSG parameters, glycometabolism, some lipid metabolism indexes and RPE (all P<0.05), and no significantly difference in BMI [(24.3±2.7) vs (24.3±2.8) kg/m(2)] between the two groups. Compared with the low intensity subgroup, there were significant improvement in 2 hours' postprandial insulin, insulin resistance index, low density lipoprotein cholesterol, lipoprotein A, RPE, 6 MWD in moderate subgroup (P<0.05). Conclusion: Nasal CPAP combined with moderate intensity aerobic exercise can effectively improve the glucolipid metabolism, insulin resistance and exercise tolerance in patients with OSAHS and T2DM.

[Airway epithelial ATG5 suppresses asthmatic inflammation in mice].

Objective: To explore the role and mechanisms of airway epithelium-localized ATG5 in asthmatic airway injury and inflammation. Methods: CC10-rtTA/(tetO)7-cre-ATG5(f/f)(atg5(△/△)) mice and atg5(+/+) mice were randomly assigned to control and asthma groups, respectively. Mice of the asthma group were treated with house dust mite extract (HDM), and allergic inflammation, mucus hyperproduction, and markers of autophagy, apoptosis, and necroptosis were examined. Results: Airway epithelium-specific ATG5 deficiency significantly increased the number of BALF total inflammatory cells (171.25±41.50) and eosinophils (114.54±19.61), compared with the control asthma group (42.64±8.72) (P<0.01) and (18.71±7.54) (P<0.01), respectively. Histological analyses showed that airway inflammation deteriorated significantly in atg5(△/△) asthma group (2.00±0.45) compared to atg5(+/+) group (1.23±0.26) (P<0.01). Meanwhile, Th2-related cytokines and mucus production were increased in atg5(△/△) asthma group. These mice displayed enhanced necroptosis markers RIP and RIP3, while the autophagic protein LC3B and apoptotic markers caspase-9 and -3 were not significantly changed. Conclusion: Airway epithelium-localized ATG5 suppresses allergic airway inflammation, likely via modulation of necroptosis, while independent of autophagy and apoptosis.

Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.

SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergic mice. Blockade of SHP2 function by SHP2 inhibitor PHPS-1 or conditional shp2 knockdown by adenovirus-inhibited bone-marrow-derived eosinophil differentiation in vitro, with no detectable effects on the apoptosis of eosinophils. Furthermore, SHP2 induced eosinophil differentiation via regulation of the extracellular signal-regulated kinase pathway. Myeloid shp2 conditional knockout mice (LysM(cre)shp2(flox/flox)) failed to induce eosinophilia as well as airway hyper-responsiveness. The SHP2 inhibitor PHPS-1 also alleviated eosinophilic airway inflammation and airway hyper-responsiveness, accompanied by significantly reduced levels of systemic eosinophils and eosinophil lineage-committed progenitors in allergic mice. We demonstrate that inhibition of eosinophil development is SHP2-dependent and SHP2 is sufficient to promote eosinophil formation in vivo. Our data reveal SHP2 as a critical regulator of eosinophil differentiation, and inhibition of SHP2 specifically in myeloid cells alleviates allergic airway inflammation.

Protein tyrosine phosphatase SHP2 regulates TGF-ß1 production in airway epithelia and asthmatic airway remodeling in mice.

BACKGROUND: Transforming growth factor (TGF)-ß1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF-ß1 production and thus a potential regulator of airway remodeling. OBJECTIVES: To define the signal event by which SHP2 regulates asthmatic responses in airway epithelial cells by using a mouse model of experimental OVA-induced airway remodeling. METHODS: The airways of Shp2(flox/flox) mice were infected with recombinant adenovirus vectors expressing a Cre recombinase-green fluorescence protein (GFP) fusion protein as part of allergen provocation studies using mice sensitized with ovalbumin (OVA) and repeatedly challenged with OVA. Several endpoint pathologies were assessed, including airway hyper-responsiveness (AHR), lung inflammatory score, peribronchial collagen deposition, and α-smooth muscle actin (SMA) hyperplasia. In vitro studies using airway epithelial cells (BEAS-2B) were used to investigate the role of SHP2 in the regulation of pulmonary remodeling events, including the expression of collagen, α-SMA, and TGF-ß1. RESULTS: Chronic OVA challenges in wild-type mice resulted in airway remodeling and lung dysfunction (e.g., increased inflammatory scores, collagen deposition (fibrosis), smooth muscle hyperplasia, and a significant increase in AHR). These endpoint pathology metrics were each significantly attenuated by conditional shp2 gene knockdown in airway epithelia. In vitro studies using BEAS-2B cells also demonstrated that the level of TGF-ß1 production by these cells correlated with the extent of shp2 gene expression. CONCLUSIONS: SHP2 activities in airway epithelial cells appear to modulate TGF-ß1 production and, in turn, regulate allergic airway remodeling following allergen provocation. CLINICAL IMPLICATIONS: Our findings identify SHP2 as a previously underappreciated contributor to the airway remodeling and lung dysfunction associated with allergen challenge. As such, SHP2 represents a potentially novel therapeutic target for the treatment of asthmatics. CAPSULE SUMMARY: Airway epithelial protein tyrosine phosphatase SHP2 appears to modulate TGF-ß1 activities as part of one or more cellular pathways leading to regulating the airway remodeling and lung dysfunction occurring in mouse models of allergic respiratory inflammation.

Epithelial neutrophil-activating peptide-78 recruits neutrophils into pleural effusion.

The aim of this study was to investigate the presence of epithelial neutrophil-activating peptide (ENA)-78 in pleural effusions, as well as the chemoattractant activity of pleural ENA-78 on neutrophils. Pleural effusion and serum samples were collected from 75 patients who presented to the respiratory institute (19 with malignant pleural effusion, 21 with tuberculous pleural effusion, 18 with infectious pleural effusion and 17 with transudative pleural effusion). The concentrations of ENA-78, myeloperoxidase and neutrophil elastase were determined, and the chemoattractant activity of ENA-78 for neutrophils both in vitro and in vivo was also observed. The concentrations of ENA-78, myeloperoxidase and neutrophil elastase in infectious pleural effusion were significantly higher than those in malignant, tuberculous and transudative groups, respectively (all p<0.01). Infectious pleural fluid was chemotactic for neutrophils in vitro and anti-ENA-78 antibody could partly inhibit these chemotactic effects. Intrapleural administration of ENA-78 produced a marked progressive influx of neutrophils into pleural space. Compared with noninfectious pleural effusion, ENA-78 appeared to be increased in infectious pleural effusion. Our data suggested that ENA-78 was able to induce neutrophil infiltration into pleural space and might be responsible for pleural neutrophil degranulation.

The interfacial structure and Young's modulus of peptide films having switchable mechanical properties.

We report the structure and Young's modulus of switchable films formed by peptide self-assembly at the air-water interface. Peptide surfactant AM1 forms an interfacial film that can be switched, reversibly, from a high- to low-elasticity state, with rapid loss of emulsion and foam stability. Using neutron reflectometry, we find that the AM1 film comprises a thin (approx. 15A) layer of ordered peptide in both states, confirming that it is possible to drastically alter the mechanical properties of an interfacial ensemble without significantly altering its concentration or macromolecular organization. We also report the first experimentally determined Young's modulus of a peptide film self-assembled at the air-water interface (E=80MPa for AM1, switching to E<20MPa). These findings suggest a fundamental link between E and the macroscopic stability of peptide-containing foam. Finally, we report studies of a designed peptide surfactant, Lac21E, which we find forms a stronger switchable film than AM1 (E=335MPa switching to E<4MPa). In contrast to AM1, Lac21E switching is caused by peptide dissociation from the interface (i.e. by self-disassembly). This research confirms that small changes in molecular design can lead to similar macroscopic behaviour via surprisingly different mechanisms.

Ectopic expression of IL-5 identifies an additional CD4(+) T cell mechanism of airway eosinophil recruitment.

CD4(+) T cells have a critical role in the development of allergic pulmonary inflammation, including the recruitment of eosinophils to the airway lumen and interstitium. The expression of interleukin (IL)-5 by CD4(+) cells has, in particular, often been lionized as the central link between allergic inflammation and the concomitant expansion or recruitment of eosinophils. The mechanism(s) by which CD4(+) T cells mediates eosinophil recruitment was assessed with gene knockout mice deficient for T cells or T cell subtypes and a unique IL-5 transgenic mouse (line NJ.1726) that constitutively overexpresses this cytokine in the lung epithelium. Pulmonary IL-5 expression is significantly attenuated in T cell- and CD4(+) but not CD8(+) cell-deficient animals, suggesting an obvious explanation for the lack of eosinophils in the lungs of T cell-deficient and CD4(-/-) mice. However, although the constitutive expression of IL-5 in the lung epithelium of NJ.1726 mice elicited an eosinophilia in the airway lumen of both naive and ovalbumin-treated mice, in the absence of CD4(+) cells, allergen-mediated eosinophil recruitment to the bronchoalveolar lavage fluid was abolished. Moreover, intranasal instillation of the potent eosinophil-specific chemokine eotaxin-2 was incapable of eliciting eosinophil recruitment in naive and ovalbumin-treated NJ.1726 CD4(-/-) mice, suggesting that eosinophil trafficking during allergic inflammatory responses is a consequence of a CD4(+) cell-mediated event(s) in addition to IL-5 expression and the establishment of a pulmonary chemokine gradient.

Identification and characterization of a SET/NAP protein encoded by a brain-specific gene, MB20.

A new member of the NAP/SET gene family, named MB20, was isolated from a mouse brain cDNA library by virtue of its CAG trinucleotide repetitive sequence and a brain-specific gene expression pattern. The complementary DNA sequence predicted an open reading frame of 545 amino acids, with four copies of an 11-amino-acid direct repeat. The consensus sequence for these repeats, PKE-P--K-EE, is present in the largest subunit of murine neurofilament (NF-H). The MB20 protein sequence is homologous to nucleosome assembly proteins of several species, and its C-terminus is homologous to SET proteins. Immunoblot analysis revealed that MB20 protein is expressed in the brain. Transient transfection and immunofluorescence microscopy demonstrated that MB20 is distributed in the cytoplasm as well as in the nucleus. Deletion of the N-terminal end imparts the complete localization of MB20 protein to the nucleus. The ability of MB20 to bind histone proteins was analyzed by sucrose gradient sedimentation and by retention of histone proteins by immobilized MB20 protein. On the basis of its expression pattern, predicted sequence, and protein properties, we propose that MB20 plays a unique role in modulating nucleosome structure and gene expression during brain development.

Molecular cloning and characterization of a human brain-specific gene implicated in neuronal differentiation.

A 2.5 kb human cDNA clone containing a CAG trinucleotide repeat, designated HB20, was isolated from a human fetal brain library. Northern analysis on multi-tissue blots and various cell lines confirmed that HB20 is specifically expressed in the brain. Its expression is low in two glioma cells, moderate in a neuron precursor cell, NT2, but absent in lymphoma, cervical carcinoma, or colonic carcinoma cells. Significant increase of HB20 mRNA was shown along with retinoic acid-induced terminal differentiation of NT2 cells into neuron cells, hNT. Homology comparison of the predicted HB20 amino acid sequence with the current database revealed that it belongs to a newly recognized protein family composed of nucleosome assembly proteins and SET proto-oncogene, which has been shown to interact specifically with B-type cyclins involved in the control of cell proliferation. Together with the detection of nuclear localization signals and apparent nuclear distribution of expressed protein, HB20 is likely to be a brain-specific nuclear protein, functioning in the process of neuronal differentiation.

[Clinical significance of human basophil releasability in bronchial asthma].

Human basophil releasability (HBR) was determined in 50 patients with asthma by modified human basophil degranulation test (HBDT). The result of HBDT was expressed as degranulation index (DI). 1. Anti-IgE-induced HBR: the mean value of DI in extrinsic asthma, intrinsic asthma and control subjects was 50.1 +/- 2.26(%), 32.2 +/- 2.3(%) and 18 +/- 2.74(%) (x +/- sem) respectively. If a DI of 30% or greater was considered as positive, the positive rate in the above three groups would be 96.9%, 60.0% and 20.0% respectively. There was significant difference between any two of the three groups (P less than 0.01). 2. Allergen-induced HBR: HBDT was performed in the asthmatics with sixteen allergens and in the controls with mite allergen. The positive rates were 68% in the patients and 0% in the controls. The coincident rate of the results between HBDT and skin test reached 82.9%. The results showed that anti-IgE-induced HBR could be regarded as an objective parameter for differentiating extrinsic and intrinsic asthma and allergen-induced HBR could be considered as an useful means for in vitro allergen diagnosis of asthma.

Susceptibility genetics of systemic lupus erythematosus.

The etiology of systemic lupus erythematosus (SLE) is determined in part by genetic factors which influence susceptibility to the disease. These factors presumably have a major role in determining the clinical and laboratory manifestations of SLE. Certain newer observations which may pertain to an understanding of the genetic basis of SLE will be critically reviewed in this chapter. These observations are based on advances in the analysis of human SLE and the increased knowledge provided by various murine models of human autoimmune processes. However, the specific genes involved and the mechanisms by which they exert their effect are at present still unknown. Special attention will be given newer insights into the role of genes of the major histocompatibility complex (MHC) and their relationship to the genes encoding the T cell antigen receptor. The role of classic immunoglobulin genes as well as more complex mechanisms involving preferential maternal or paternal genetic effects are also discussed. The contribution of genes encoding complement and complement receptors toward the expression of the disease state are discussed in brief.

Strong association of rheumatoid arthritis with the presence of a polymorphic Ia epitope defined by a monoclonal antibody: comparison with the allodeterminant DR4.

Among individuals with rheumatoid arthritis the presence of the polymorphic Ia antigen epitope detected by the monoclonal antibody 109d6 is more strongly correlated with disease susceptibility than are other specificities, such as HLA DR4, DRw53 (MT3) or the antigenic determinant, defined by the monoclonal antibody 17-3-3S. The cells of 93% of Caucasian and Hispanic patients react with the 109d6 reagent. As was the case in normal individuals, all DR4-positive patients express the 109d6 determinant; however, 26% of those with rheumatoid arthritis have the epitope recognized by antibody 109d6, but lack the specificity DR4. Of these, one-third expresses only HLA DR1 and DQw1 (MT1, MB1) determinants. Studies of family members reveal that here the determinants 109d6, DR1, and DQw1 are encoded by the same unusual haplotype. In certain other individuals with rheumatoid arthritis who express DR4, DRw53, and the 109d6 determinants, family studies show that the 109d6 epitope is encoded not only by the haplotype specifying DR4 but also by the opposite haplotype that does not bear the genes for DR4. This suggests that homozygosity for certain Ia epitopes is relevant to determining the disease-susceptibility state. These studies emphasize the utility of monoclonal antibodies as reagents for the recognition of Ia epitopes that are more closely involved in the determination of disease susceptibility than are allomorphic molecules detected by conventional typing alloantisera.

Functional subsets of human monocytes defined by monoclonal antibodies: a distinct subset of monocytes contains the cells capable of inducing the autologous mixed lymphocyte culture.

The induction of most immune responses requires the close cooperation between T cells and antigen-presenting cells (APC), presumably of monocyte/macrophage (M phi) lineage. To characterize human APC further, we used two monoclonal antibodies, OKM1 and OKM5, to isolate and identify M phi subsets. OKM1 has been described and recognizes cell surface antigens on most M phi and granulocytes. OKM5 recognizes cell surface determinants present on the majority of human M phi but does not recognize other hematopoietic cell types. A small subset of peripheral blood M phi is OKM1-OKM5+. Human peripheral blood E- cells were separated into OKM1+ and OKM1- subsets by a rosetting technique utilizing anti-Ig-coated red cells. The capacity to present self antigens in the autologous mixed lymphocyte culture (AMLC) resided predominantly within the E-OKM1- subset, even if surface membrane Ig-positive cells were eliminated. Similar experiments showed that the ability to stimulate in AMLC was contained in the E-OKM5+ population and in fact resided primarily within the E-OKM1-OKM5+ subset. All of these subsets were able to trigger allogeneic T cells to proliferate. The capacity of these APC subsets to present soluble antigens (mumps, tetanus toxoid) was also examined. The data demonstrated that although the majority of these APC are E-OKM1+, E-OKM1-OKM5+ cells can also present foreign antigen. Taken together, these data suggest OKM1 and OKM5 can be used to isolate two functionally distinct human M phi subsets. One subset (E-OKM1+) is capable of presenting soluble antigens but shows minimal ability to trigger AMLC. The other subset (E-OKM1-OKM5+) can also present soluble antigens but is the predominant subset that can trigger AMLC.