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Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer. Objective: To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection. Methodology: CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018). Results: There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004). Conclusion: Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.
ABSTRACT
A microbiota e o sistema imune do idoso apresentam algumas alterações, favorecendo ao aparecimento de infecções e doenças inflamatórias. A doença periodontal é um exemplo, permeando entre fase imediata e tardia, pode ter alterações em sua evolução com o envelhecimento humano. Compreender a doença periodontal e sua relação com o ciclo da vida é importante para a prevenção, tratamento e cura. Este estudo tem como objetivo avaliar a quantidade de mastócitos (triptase), células dendríticas imaturas (CD1a), células dendríticas maduras (CD83) e vasos sanguíneos (CD34) em 154 tecidos periodontais saudáveis e doentes (27 idosos e 127 adultos). Foi utilizada a técnica de imunoistoquímica através da imunomarcação do CD1a, CD83, triptase e CD34, sendo contabilizados em 5 campos de maior número de células positivas, no aumento de 1000x. Para o CD34, ainda foram calculadas a área e o perímetro microvascular para todos os vasos sanguíneos presentes, e dos vasos com presença do endotélio vascular alto. Não houve diferença na imunomarcação das células dendríticas, dos mastócitos e na quantidade de vasos sanguíneos nos tecidos gengivais, entre os casos de gengiva clinicamente saudável, gengivite induzida por biofilme e periodontite estágios II, III e IV, avaliando isoladamente os grupos etários: adultos e idosos. As células dendríticas imaturas são mais numerosas no idoso com o quadro clínico de gengivite e periodontite. Os adultos com gengivite induzida por biofilme possuem maior quantidade de vasos sanguíneos que o grupo idoso. A área microvascular e o perímetro microvascular dos vasos sanguíneos com o endotélio vascular alto apresentaram maiores nos idosos nos casos de gengivite. Este estudo concluiu que nesta amostra não houve diferença na quantidade de células dendríticas imaturas e maduras, mastócitos na doença periodontal dentro dos grupos etário, porém as células dendríticas imaturas estão mais presentes no idoso podendo estar relacionado a algum decréscimo funcional. Em relação aos vasos sanguíneos, há presença de HEVs em adultos e idosos, não havendo diferença entre os diagnósticos. Nos idosos com gengivite há um aumento da área microvascular e perímetro microvascular, necessitando de estudos que justifiquem esta diferença (AU).
The elderly's microbiota and immune system show some changes, favoring the onset of infections and inflammatory diseases. Periodontal disease is an example, permeating between immediate and adaptative stages, it can have changes in its evolution with human aging. Understanding periodontal disease and its relationship with the life cycle is important for prevention, treatment and cure. This study aims to assess the amount of mast cells (tryptase), immature dendritic cells (CD1a), mature dendritic cells (CD83) and blood vessels (CD34) in 154 healthy and sick periodontal tissues (27 elderly and 127 adults). The immunohistochemistry technique was used through the immunostaining of CD1a, CD83, tryptase and CD34, being counted in 5 fields with a greater number of positive cells, in the 1000x increase. For CD34, the microvascular area and perimeter were also calculated for all blood vessels present, and for vessels with the presence of high vascular endothelium. There was no difference in the immunostaining of dendritic cells, mast cells and the amount of blood vessels in the gingival tissues, between cases of clinically healthy gingiva, biofilm-induced gingivitis and stages II, III and IV periodontitis, evaluating the age groups: adults and elderly. Immature dendritic cells are more numerous in the elderly with the clinical picture of gingivitis and periodontitis. Adults with biofilm-induced gingivitis have a greater amount of blood vessels than the elderly group. The microvascular area and the microvascular perimeter of the blood vessels with the high vascular endothelium were larger in the elderly in cases of gingivitis. This study concluded that in this sample there was no difference in the amount of immature and mature dendritic cells, mast cells in periodontal disease within the age groups, however, immature dendritic cells are more present in the elderly and may be related to some functional decrease. Regarding blood vessels, there are HEVs in adults and the elderly, with no difference between diagnoses. In the elderly with gingivitis there is an increase in the microvascular area and microvascular perimeter, requiring studies that justify this difference (AU).
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Periodontal Diseases/pathology , Dendritic Cells/pathology , Aged , Antigens, CD34 , Tryptases , Immunohistochemistry , Chi-Square Distribution , Statistics, NonparametricABSTRACT
Abstract The aim of this study was to determine if the distribution of Langerhans cells (LC) and interstitial dendritic cells (IDC) is altered in AIDS-associated oral Kaposi's sarcoma when compared to HIV-negative highly vascular oral lesions. Fifty-one cases of AIDS-associated oral Kaposi's sarcoma and 20 of highly vascular oral lesions were retrospectively retrieved. All cases of Kaposi's sarcoma were confirmed with immunoreactions against CD34 and HHV-8. Clinical data regarding sex, age and lesions location were obtained from pathology reports. Immunohistochemistry against CD207 (immature dendritic cells) and CD83 (mature dendritic cells) were done. LC were in the epithelium and IDC in the stroma. CD207+ cells predominated in the epithelium of the lesions, whereas CD83+ cells predominated in their stromal compartment. Kaposi's sarcoma had a lower CD207+ immature LC count (p=0.02) and an increased CD207+ IDC than highly vascular oral lesions (p<0.001). Moreover, Kaposi's sarcoma also showed an increased number of mature CD83+ IDC than highly vascular oral lesions (p<0.001). There were significant alterations in the distribution of LC and IDC in AIDS-associated Kaposi's sarcoma when compared to HIV-negative vascular oral lesions, suggesting that changes in their concentrations may play a role in the pathogenesis of Kaposi's sarcoma.
Resumo O objetivo deste estudo foi determinar se a distribuição das células de Langerhans (CL) e das células dendríticas intersticiais (CDI) está alterada no sarcoma de Kaposi oral associado à AIDS quando comparado às lesões orais altamente vasculares HIV-negativas. 51 casos de sarcoma de Kaposi oral associado à AIDS e 20 de lesões orais altamente vasculares foram recuperados retrospectivamente. Todos os casos de sarcoma de Kaposi foram confirmados pela positividade para os anticorpos CD34 e HHV-8. Dados clínicos sobre sexo, idade e localização das lesões foram obtidos dos laudos histopatológicos. Foram realizadas imunoistoquímica contra CD207 (células dendríticas imaturas) e CD83 (células dendríticas maduras). As CL estavam presentes no epitélio enquanto as CDI estavam presentes no estroma. As células CD207+ predominaram no epitélio das lesões, enquanto as células CD83+ predominaram no estroma. O sarcoma de Kaposi teve uma contagem mais baixa de CD imaturas CD207+ (p = 0,02) e número aumentado de CDC CD207+ do que lesões orais altamente vasculares (p<0,001). Além disso, o sarcoma de Kaposi também mostrou um número aumentado de CDI CD83+ maduras do que lesões orais altamente vasculares (p<0,001). Houve alterações significativas na distribuição de CL e CDI no sarcoma de Kaposi associado à AIDS quando comparado às lesões orais vasculares HIV-negativas, sugerindo que alterações na distribuição das mesmas podem desempenhar um papel na patogênese do sarcoma de Kaposi.
Subject(s)
Humans , Sarcoma, Kaposi , Acquired Immunodeficiency Syndrome , Herpesvirus 8, Human , Dendritic Cells , Retrospective StudiesABSTRACT
Objective To investigate the number and distribution of dendritic cells in normal endometrium of reproductive age during the normal menstrual cycle .Methods Normal endometrial samples were collected from 40 women of reproductive age . 20 endometrium samples at the proliferative phase (day 6th to 10th) and 20 endometrium samples at the window of implantation(day 20th to 24th) were obtained .These patients underwent intrauterine exploration before IVF and ET resulting from tubal resec-tion or male factor infertility .Endometrial tissue was collected with a pipelle aspirator .Sections were stained with hematoxylin-eosin (HE) to identify the morphological characteristics of endometrial tissues .The Envision two-step immunohistochemical staining technique was used to detect the expression of CD1a and CD83 in the endometrium .Normal human skin and tonsil were used as pos-itive control tissues for CD1a and CD83 ,respectively .The serum levels of ovarian steroid hormones were measured to analyze their relationship with the expression of CD1a and CD83 .Results CD1a + DCs were found in all samples of window of implantationand most samples of the proliferative phase (18/20 ,90% ) .DCs showed irregular shape with different processes and were buffy in cell membrane ,mainly in stroma around grand and blood vessels .The density of CD1a + DCs at the window of implantation were (18 .2 ± 5 .76)cells/mm2 ,significantly higher than that at the proliferative phase [(6 .5 ± 4 .05)cells/mm2 ,P 0 .05) .Conclusion Increased CD1a+ immature DCs at the window of implantation in endometri-um may play an important role in the establishment of maternal-fetal tolerance .
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Objective To investigate the infiltration of dendritic cell (DC) in Vocal cord polyp, laryngeal leukopla-kia and glottic squamous cell carcinoma,and to observe laryngeal mucosal lesions of the state of the immune microenviron-ment, and to research significance of DC on the development of glottic squamous cell carcinoma. Methods The infiltration of S-100+and CD83+DC in 20 cases of Vocal cord polyp, 47 cases of laryngeal leukoplakia, 45 cases of glottic squamous cell carcinoma tumor and 20 cases of laryngeal normal mucosa were examined using immunohistochemistry. Results The num-ber of S-100+and CD83+DC were significantly higher in glottic squamous cell carcinoma, laryngeal leukoplakia and vocal cord polyp than that in laryngeal normal mucosa (P<0.05). The number of S-100+and CD83+DC were higher in laryngeal leukoplakia than that in glottic squamous cell carcinoma (P<0.05). The number of S-100+and CD83+DC in mild dysplasia and moderate dysplasia were less than that in severe atypical hyperplasia (P<0.01). In glottic squamous cell carcinoma, S-100+ and CD83+DC with poor-differentiated was significantly less than that with well-differentiated (P < 0.01). Conclu-sion Changes in the number of dendritic cell was found in vocal cord polyp, laryngeal leukoplakia and glottic squamous cell carcinoma, which indicated that there were an abnormal immune status. Changing of dendritic cell in laryngeal mucosa plays an important role in laryngeal cancer development.
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AIM: To prepare and characterize a novel anti-human CD83 monoclonal mAb. METHODS: Female BALB/c mice of 6-8 weeks old were immunized with CD83 transfectant (L929/CD83) as immunogen. The spleen B cells of the mice were fused with Sp2/0 myeloma cells. The hybridoma cells were screened with CD83 transfectant (L929/CD83 and 293/CD83) by FCM. The biological characteristics of antibody were investigated by rapid isotyping analysis, karyotype analysis, competitive inhibition test and Western blot. RESULTS: One hybridoma cell line named 9D8 was obtained, which had the property of secreting antihuman CD83 monoclonal antibody steadily, This mAb specifically recognized CD83 molecule expressed on human mature DC, activated T cells, and tumor cell line Daudi, myeloma cell line 8226. This mAb can recognize a distinct epitope from comercial mAb(HB15e). CONCLUSION: One hybndoma cell line has been developed successfully, which may lay a fundation for further study on the function of this molecule.
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Objective To investigate the expression and clinical significance of tumor infiltrating dendritic cells(TIDCs) within gastric tumor tissues.Methods Immunohistochemistry(IHC),in-situ hybridization(ISH) and flow cytometry were applied to detect the expression of S100,CD83 mRNA and CD83 on DCs in 45 gastric adenocarcinoma tissues.The co-relationship of the S100 and CD83 expression with clinical(pathological) features was analyzed.Results IHC showed that S100 expression was unevenly distributed(within) 42 cancer tissue and CD83 was only expressed in tumor-adjacent tissue and normal tissue.ISH showed that CD83 mRNA was limitedly expressed within 7 samples.S100 expression had no significant(correlation) with clinical pathological features,while CD83 reversely correlated with TNM stages.Detected by flow cytometry,CD83 was expressed in low level in all 45 gastric cancer tissues and negative correlations were found with lymph node metastasis and TNM stages of gastric cancer(r=-0.879,P
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Dendritic cells (DC) are highly efficient antigen-presenting cells that initiate the primary immune response. Several laboratories have developed culture systems for human DC from peripheral blood monocytes. Most of these studies have used fetal calf serum (FCS) containing culture conditions that are inappropriate for human application. GM-CSF and IL-4 were used to make immature DC. The monocyte-conditioned medium (MCM) was used to induce the final maturation of DC. Using the previously described methods, the quality of MCM has unpredictable variations. Therefore using a defined cocktail of growth factors for the generation of mature DC would be advantageous for experimental as well as clinical purposes. In this study, it is suggested that combinations of both GM-CSF/IL-4 or GM-CSF/IL-13 could be used as the first-step culture to produce immature DC, and that cytokine cocktail (GM-CSF, IL-4, IL-1beta, TNF-alpha, IL-6, PGE2) was as efficient as MCM for the second step-culture to produce fully maturated DC. Here, we have generated an easily reproducible culture system for DC that allows for the generation of large amounts of immature and mature DC, and we also now have established the method in a FCS-free system that is suitable for clinical use.