scholarly journals Immunohistochemical Expression Patterns of Inflammatory Cells Involved in Chronic Hyperplastic Candidosis

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 232 ◽  
Author(s):  
Ailish Williams ◽  
David Williams ◽  
Helen Rogers ◽  
Xiaoqing Wei ◽  
Michael Lewis ◽  
...  

The profile of the inflammatory cell infiltrate in chronic hyperplastic candidosis (CHC) was determined in oral mucosal biopsies by immunohistochemistry. One tonsillar tissue section was included as an immunohistochemistry control, whilst squamous papilloma (n = 4) with secondary Candida infection was used as Candida controls. Oral lichen planus tissues (n = 10) provided negative controls for Candida presence, as well as positive controls for inflammation. Immunohistochemistry employed antibodies specific for CD3+ (T lymphocytes), CD4+ (T helper cells), CD8+ (cytotoxic T cells), and CD20+ (B lymphocytes). Manual counting of stained cells from digitised images determined the proportion of each cell type relative to the total number of cells, and these were assessed in the mucosa, the epithelium, and the lamina propria. The mean proportion of CD3+ cells was significantly higher than CD20+ cells in all tissue types. For CHC, the mean proportion of CD3+ cells in entire tissues was 15.6%, with the highest proportion in the lamina propria (32.6%) compared with the epithelium (3.9%). CD20+ cells were in much lower proportions (1.8%) in CHC, with the highest proportion (3.6%) in the lamina propria. T lymphocytes were predominately CD4+ cells (9.0%) compared with CD8+ cells (4.4%). CD4+ cells were most prevalent in the lamina propria (23.1%) compared with the epithelium (mean = 3.2%). From these results, it was concluded that the immune response invoked by Candida in CHC is primarily driven by the T helper cells.

2016 ◽  
Vol 15 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Norihiro Ueda ◽  
Rong Zhang ◽  
Minako Tatsumi ◽  
Tian-Yi Liu ◽  
Shuichi Kitayama ◽  
...  

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 850-857 ◽  
Author(s):  
Andreas Heitger ◽  
Nikolaus Neu ◽  
Hannelore Kern ◽  
Eva-Renate Panzer-Grümayer ◽  
Hildegard Greinix ◽  
...  

Abstract To contribute to the understanding of the role of the thymus in humans in the reconstitution of naive (CD45RA+) T cells after bone marrow transplantation (BMT), we compared T-cell regeneration in a unique situation, namely a thymectomized cancer patient (15 years old), with that of thymus-bearing patients after allogeneic BMT. These cases shared features of transplantation (total body irradiation, HLA-matched donors, and graft-versus-host disease prophylaxis with cyclosporine A) and all had an uncomplicated posttransplantation course. As shown by fluorescence-activated cell sorting analyses, the thymectomized host failed to reconstitute CD45RA+ T-helper cells even 24 months after BMT (11% CD45RA+ of CD4+ cells). In this patient, preferentially CD45RO+ cells contributed to the recovery of CD4+ cells (206 of 261/μL at 6 months and 463 of 558/μL at 24 months after BMT, CD45RA+ of CD4+ cells), whereas CD45RA+ cells remained low (<60/μL). In contrast, nine thymus-bearing hosts (5 children and 4 adults) examined between 6 and 24 months after BMT effectively reconstituted CD4+/CD45RA+ cells according to their normal age-related range (≥28% in adults and ≥50% in children). Five of these were analyzed sequentially at 6 and 9 months after BMT. Within this period, CD45RA+ cells increasingly contributed to the recovery of CD4+ cells (median, +21%), even when total CD4+ cells decreased. With respect to T-cytotoxic/suppressor cells, the thymectomized host retained the capacity to recover CD45RA+ cells (137 of 333/μL at 6 months and 596 of 1,046/μL at 24 months after BMT, CD45RA+ of CD8+ cells), a proportion similar to that seen in thymus-bearing hosts. These findings suggest that a thymus-independent pathway exists to regenerate CD45RA+ T-cytotoxic/suppressor cells, but residual thymus is essential to reconstitute naive (CD45RA+) T-helper cells after BMT in humans.


2016 ◽  
Vol 18 (3(71)) ◽  
pp. 45-49
Author(s):  
I.P. Кrytsia

To maintain a body at sufficient physiological level the effective functioning of the immune system, which determines the resistance and immune reactivity of animals, is necessary. In our studies in newborn foals indicators of cellular immunity were mature. During the studying of foals of all ages were established the reduction of hematological parameters in animals months of age.The use of immunomodulators prevents the immunodeficiency in animals. Immunomodulators introduction for animals normalizes T–immune system, in particular, increases the number of leucocytes in the blood, lymphocytes of certain populations, especially teofilin–resistant subpopulation of T–helper cells, increases the functional activity of lymphocytes.Under influence of ribotan revealed a trend to the increasing of T–lymphocytes by 0.2 – 1.2% (0.4 – 2.3%), respectively in Purebred Saddle and Ukrainian Saddle breeds. Results of the content of T–helper and T–suppressor cells in foals blood after ribotan administration showed that the use of immunomodulators not only increases the number of T–helper cells, but restores the ratio T–h / T–s, which returned to the optimal rate (1.9). Analyzing the functional status of T–lymphocytes during the application of immunomodulators was found the probable increase of the number of activated T–lymphocytes in Purebred Saddle foals more than 2–fold (P <0.01) and trend to increase of these cells in Ukrainian Saddle foals. In relation to thermostable T–lymphocytes, was note that the trend to the most optimal level of these cells installed in foals after administration of ribotan (values within 3 – 4%). The increasing in number of thermostable T–cells more than 4% indicates an increase power of suppressor T–cells population, indicating the inhibition of T–helper cells, and therefore the production of antibodies. Thus, the use of ribotan in dose of 1 ml / animal for three days leads to an increasing in 1.4 – 4.5% of the number of leukocytes in the blood of experimental group of foals compared with control animals. Under influence of ribotan in the blood of foals increases cell (number of T–lymphocytes in 0.4 – 2.3%) and functional activity (T–active lymphocytes in 2.3 times; P < 0.05) T–immune system. Under influence of cycloferon in the blood of foals increases the functional activity of T–immune system (the number of T–active lymphocytes in 16.7 – 25%; P < 0.05). 


1998 ◽  
Vol 72 (6) ◽  
pp. 4866-4873 ◽  
Author(s):  
Bertram T. Ober ◽  
Artur Summerfield ◽  
Christina Mattlinger ◽  
Karl-Heinz Wiesmüller ◽  
Günther Jung ◽  
...  

ABSTRACT Pseudorabies virus (PRV; suid herpesvirus 1) infection causes heavy economic losses in the pig industry. Therefore, vaccination with live attenuated viruses is practiced in many countries. This vaccination was demonstrated to induce extrathymic virus-specific memory CD4+CD8+ T lymphocytes. Due to their major histocompatibility complex (MHC) class II-restricted proliferation, it is generally believed that these T lymphocytes function as memory T-helper cells. To directly prove this hypothesis, 15-amino-acid, overlapping peptides of the viral glycoprotein gC were used for screening in proliferation assays with peripheral blood mononuclear cells of vaccinated d/d haplotype inbred pigs. In these experiments, two naturally processed T-cell epitopes (T1 and T2) which are MHC class II restricted were identified. It was shown that extrathymic CD4+CD8+ T cells are the T-lymphocyte subpopulation that responds to epitope T2. In addition, we were able to show that cytokine secretion can be induced in these T cells through recall with inactivated PRV and demonstrated that activated PRV-primed CD4+CD8+ T cells are able to induce PRV-specific immunoglobulin synthesis by PRV-primed, resting B cells. Taken together, these results demonstrate that the glycoprotein gC takes part in the priming of humoral anti-PRV memory responses. The experiments identified the first T-cell epitopes so far known to induce the generation of virus-specific CD4+CD8+ memory T lymphocytes and showed that CD4+CD8+ T cells are memory T-helper cells. Therefore, this study describes the generation of virus-specific CD4+CD8+ T cells, which is observed during vaccination, as a part of the potent humoral anti-PRV memory response induced by the vaccine.


2020 ◽  
Vol 8 (1) ◽  
pp. e000469 ◽  
Author(s):  
Laura-Sophie Landwehr ◽  
Barbara Altieri ◽  
Jochen Schreiner ◽  
Iuliu Sbiera ◽  
Isabel Weigand ◽  
...  

BackgroundAdrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy.MethodsWe performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3+), T helper cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+) and regulatory T cells (Tregs; CD3+CD4+FoxP3+) in 146 ACC tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data of immune cell infiltration were correlated with clinical data (including glucocorticoid excess).Results86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.3%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95% CI 0.25 to 0.87), which was true for CD4+− and CD8+subpopulations as well. In localized, non-metastatic ACC, the favorable impact of TILs on overall and recurrence-free survival was manifested even independently of ENSAT (European Network for the Study of Adrenal Tumors) stage, resection status and Ki67 index. T helper cells were negatively correlated with glucocorticoid excess (Phi=−0.290, p=0.009). Patients with glucocorticoid excess and low TILs had a particularly poor overall survival (27 vs. 121 months in patients with TILs without glucocorticoid excess).ConclusionGlucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.


1995 ◽  
Vol 5 (7) ◽  
pp. 1441-1450
Author(s):  
A Shoker ◽  
R Miller ◽  
R Uldall ◽  
E Friedman ◽  
S Angra ◽  
...  

Some uremic patients with a history of blood transfusion, pregnancy, and previous transplantation maintain high levels of alloreactive cytotoxic antibodies in the absence of continuous exogenous allogenic stimuli and are thus considered sensitized to the major histocompatibility proteins. To differentiate into antibody-producing cells, B lymphocytes must interact with T-helper (CD4+) cells. Whether ongoing help from these cells is necessary for the B cells to continue producing cytotoxic alloreactive antibodies in these sensitized uremic patients is unknown. To gain insight into the cellular mechanisms that are associated with sustained alloantibody production, T cell activation markers were measured and specific and nonspecific T-helper cell function was studied in three uremic groups with different levels of panel reactive antibodies: 10 patients whose sera reacted to more than 80% of a panel of normal lymphocytes for at least 6 months before the study were highly sensitized, 20 patients whose sera reacted to less than 80% of the panel were moderately sensitized, and 10 nonsensitized patients whose sera did not react to any cell on the panel. The number of total and activated T-helper cells was similar in the highly sensitized and nonsensitized patients. Peripheral blood lymphocyte proliferation in response to plant lectins, soluble OKT3, or alloantigens was similar in the three uremic groups. The spontaneous proliferation of pure T-helper cells and proliferative responses to immobilized OKT3 or alloantigens were also similar in highly sensitized and nonsensitized patients. Alloreactive interleukin-2-producing cell frequencies with pure CD4+ cells as responding cells were 771 +/- 77.9/10(6) cells in highly sensitized, 945 +/- 252/10(6) cells in nonsensitized, and 973 +/- 114/10(6) cells in controls (P = not significant). Panel reactive antibody levels did not correlate with any of the measures of T helper responses. There was a significant decrease of peripheral blood lymphocyte responses to alloantigens and anti-CD3 antibody in all uremic patients as compared with normals, suggesting a dysfunction in accessory cells that was quantitatively similar in sensitized and nonsensitized patients. In spite of the continuous production of alloantibodies by B cells, there is no evidence of either specific or nonspecific enhancement of T-helper cell function in sensitized patients. The absence of T cell immunity to alloantigens suggests that sustained activation of T-helper cells with subsequent interleukin-2 production is not necessary to maintain alloreactive B cell function.


2016 ◽  
Vol 22 (7) ◽  
pp. 943-955 ◽  
Author(s):  
Anna K. Baumann ◽  
Jerome Schlue ◽  
Fatih Noyan ◽  
Matthias Hardtke-Wolenski ◽  
Frank Lehner ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4729-4729
Author(s):  
Polyxeni Lampropoulou ◽  
Evgenia Verigou ◽  
Argiris Symeonidis ◽  
Charalambos Gogos ◽  
Elena E. Solomou

A subpopulation of CD4+helper T cells, T-follicular helper cells (TFH), are characterized by the surface expression of CXCR5, ICOS, and PD1, the transcription factor Bcl-6, and produce mainly IL-21, but also IL-17, IL-4, and IFN-γ. They represent the major population that helps B cells to turn into plasma cells and they are implicated in the pathogenesis of different autoimmune diseases. Peripheral CXCR5+CD4+ T helper cells (p-TFH) are the circulating component of TFH. p-TFH cells have been extensively studied in the context of inflammation and autoimmunity. Patients with systemic lupus erythematosus and rheumatoid arthritis have increased p-TFH. Immune dysregulation characterizes low risk myelodysplastic syndromes (MDS). The expression of p-TFH in patients in low risk MDS has not been previously evaluated. To examine the expression of p-TFH in this disease we isolated peripheral blood mononuclear cells (PBMCs) from patients with low risk MDS (n=20, Refractory Anemia,RA; and Refractory Cytopenias with Multilineage Dysplasia, RCMD) and ten healthy, age- matched controls. Written informed consent was obtained from all study subjects. PBMCs were left untreated or activated with PMA and Ionomycin, in the presence of Brefeldin A, for 5 hours. Subsequently, cells were stained with the surface markers CXCR5, CD4, CD45RO, ICOS and intracellular IL-21, and analyzed by flow cytometry. Patients with MDS show decreased CD4+ICOS+ cells compared to healthy controls (5,34±1,44% vs 8,69±4,08% respectively, p=0.028). The median percentages of CXCR5+CD4+ cells (estimated on CD4+ cells) before stimulation were lower in MDS patients although not statistically significant different from the control subjects. The expansion of the CXCR5+CD4+ population after stimulation was higher in MDS patients compared to healthy individuals (ratio of stimulated to unstimulated CXCR5+CD4+ cells of MDS patients: 1.44±0.47 vs control: 1.23± 0.32, p=0.027). MDS patients at diagnosis showed increased median levels of IL-21 producing CXCR5+CD4+ cells compared to patients previously treated with erythropoietin (EPO), (21,34±10,14% vs 17,55±12,91, respectively). Additionally, patients with RA showed increased CXCR5+CD4+IL-21+ cells compared to the RCMD patients (22,39±11,76% vs 17,84±10,70%, respectively). Collectively, the percentage of IL-21 producing CXCR5+CD4+ cells did not differ significantly between the MDS and control groups (20,57± 10,12% vs 19,86± 11,03%, respectively). The presence of marrow fibrosis did not affect the differences observed and described above. The p-TFH cell subset was identified in every case as a memory component of CD4+ T helper cells, as previously described. Although the number of patients analyzed is limited, our results suggest that low risk MDS patients show a trend of lower CXCR5+CD4+ cells compared to age–matched control subjects. EPO treatment eliminates IL-21 production from CXCR5+CD4+ cells compared to treatment-naïve patients. Further analysis of a larger pool of subjects along with the examination of the specific transcription factor Bcl-6 will reveal the role of p-TFH cells in low risk MDS. Disclosures: No relevant conflicts of interest to declare.


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