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Haematologica Sep 2014There are no "benign lymphomas", a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of... (Review)
Review
There are no "benign lymphomas", a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH translocations associated with the in situ forms of follicular lymphoma and mantle cell lymphoma, respectively. There are other clonal B-cell proliferations with low risk of progression; these include the pediatric variants of follicular lymphoma and marginal zone lymphoma. Historically, early or incipient forms of T/NK-cell neoplasia also have been identified, such as lymphomatoid papulosis and refractory celiac disease. More recently an indolent form of T-cell lymphoproliferative disease affecting the gastrointestinal tract has been described. Usually, CD8(+), the clonal cells are confined to the mucosa. The clinical course is chronic, but non-progressive. NK-cell enteropathy is a clinically similar condition, composed of cytologically atypical NK-cells that may involve the stomach, small bowel or colon. Breast implant-associated anaplastic large cell lymphoma is a cytologically alarming lesion that is self-limited if confined to the seroma cavity. Atypical lymphoid proliferations that lie at the border of benign and malignant can serve as instructive models of lymphomagenesis. It is also critical that they be correctly diagnosed to avoid unnecessary and potentially harmful therapy.
Topics: Antigens, CD; Antineoplastic Agents; B-Lymphocytes; Biomarkers; Cell Proliferation; Clone Cells; Early Diagnosis; Gene Expression; Humans; Immunophenotyping; Lymphoma; T-Lymphocytes; Translocation, Genetic
PubMed: 25176983
DOI: 10.3324/haematol.2014.107938 -
Cell Host & Microbe Apr 2020Recombinant HIV-1 envelope (Env) glycoproteins of ever-increasing sophistication have been evaluated as vaccine candidates for over 30 years. Structurally defined mimics... (Review)
Review
Recombinant HIV-1 envelope (Env) glycoproteins of ever-increasing sophistication have been evaluated as vaccine candidates for over 30 years. Structurally defined mimics of native trimeric Env glycoproteins (e.g., SOSIP trimers) present multiple epitopes for broadly neutralizing antibodies (bNAbs) and their germline precursors, but elicitation of bNAbs remains elusive. Here, we argue that the interactions between Env and the immune system render it exceptional among viral vaccine antigens and hinder its immunogenicity in absolute and comparative terms. In other words, Env binds to CD4 on key immune cells and transduces signals that can compromise their function. Moreover, the extensive array of oligomannose glycans on Env shields peptidic B cell epitopes, impedes the presentation of T helper cell epitopes, and attracts mannose binding proteins, which could affect the antibody response. We suggest lines of research for assessing how to overcome obstacles that the exceptional features of Env impose on the creation of a successful HIV-1 vaccine.
Topics: AIDS Vaccines; Adaptive Immunity; Antibodies, Neutralizing; B-Lymphocytes; CD4 Antigens; Epitopes, B-Lymphocyte; HIV Antibodies; HIV-1; Immunity, Innate; Mannose; Membrane Glycoproteins; Molecular Mimicry; Protein Binding; Protein Multimerization; T-Lymphocytes; env Gene Products, Human Immunodeficiency Virus
PubMed: 32272076
DOI: 10.1016/j.chom.2020.03.018 -
Head and Neck Pathology Sep 2020Research on the role of B cells in the development and modulation of antitumor immunity has increased in recent years; however, knowledge about B cell phenotype and...
Research on the role of B cells in the development and modulation of antitumor immunity has increased in recent years; however, knowledge about B cell phenotype and function in tumor draining lymph nodes (TDLNs) is still incomplete. This study aimed to investigate changes in the phenotypic profile of B cells in TDLNs of head and neck squamous cell carcinoma (HNSCC) during disease progression. Mononuclear cells were isolated from TDLNs and stained with antibodies for CD19 and other B cell-related markers and analyzed by flow cytometry. CD19 B cells comprised 38.6 ± 8.9% of lymphocytes in TDLNs of HNSCC. Comparison of metastatic and non-metastatic LNs disclosed no significant differences in the frequencies of B cell subsets including antigen-experienced, naïve, switched, unswitched, atypical memory, marginal zone-like B cells, and B cells with regulatory phenotypes. The percentage of atypical memory (CD27IgMIgD) B cells was significantly higher in patients with tongue SCC with no involved LNs (p = 0.033) and correlated inversely with the number of involved LNs. The frequency of CD24CD38 B cells was significantly higher in non-metastatic LNs of patients with grade I compared to grade II (p = 0.016), and the percentage of CD5 B cells decreased as tumors progressed from stage III to IV (p = 0.008). Our data show that in TDLNs of HNSCC, the frequency of B cells with atypical memory and regulatory phenotypes was significantly associated with good prognostic factors; however, their function remains to be investigated.
Topics: Adult; Aged; Aged, 80 and over; B-Lymphocyte Subsets; B-Lymphocytes, Regulatory; Female; Humans; Immunologic Memory; Lymph Nodes; Male; Middle Aged; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 31691165
DOI: 10.1007/s12105-019-01095-1 -
Frontiers in Immunology 2023Increasing evidence indicated that schizophrenia and obesity are associated with altered mitochondrial and immune function. In this study, we investigated the levels of...
OBJECTIVE
Increasing evidence indicated that schizophrenia and obesity are associated with altered mitochondrial and immune function. In this study, we investigated the levels of CRP (C-reactive protein) and mitochondrial lymphocytes in chronically treated schizophrenia patients with atypical antipsychotic medications and further explored the relationship between mitochondrial lymphocyte and weight gain as well as cognitive function in these patients.
METHODS
We evaluated the mitochondrial lymphocyte count of 97 patients (53 overweight, 44 non-overweight) and 100 healthy controls using mitochondrial fluorescence staining and flow cytometry (NovoCyte, Agilent Technologies, US). The serum CRP was measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Clinical symptoms and cognitive function of the patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
RESULTS
The results showed that mitochondrial lymphocyte counts of CD3+ T, CD3+CD4+ T, and CD3+CD8+ T cells in schizophrenia patients were higher than in the control group (p < 0.05). Additionally, overweight patients had significantly higher mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells compared to schizophrenia patients with normal weight. Stratified analysis by gender revealed that there was a statistically significant difference in CD3+CD4+ mitochondrial lymphocyte count in male patients (p = 0.014) and a marginal trend toward significance in female patients (p = 0.058). Furthermore, the mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells, as well as CRP levels, were positively correlated with BMI in schizophrenia patients, but the mitochondrial lymphocyte counts of CD3+CD4+ T cells were negatively correlated with the language scale in the RBANS.
CONCLUSION
Our study results provide evidence for the association between altered mitochondrial T lymphocyte and weight gain as well as cognitive impairment in schizophrenia patients treated with atypical antipsychotic medications.
Topics: Humans; Male; Female; Antipsychotic Agents; Schizophrenia; Overweight; CD8-Positive T-Lymphocytes; Cognition; Weight Gain
PubMed: 38235140
DOI: 10.3389/fimmu.2023.1325495 -
Orphanet Journal of Rare Diseases Dec 2021Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype...
BACKGROUND
Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (muco-cutaneous telangiectases, arteriovenous malformations), a specific risk of infection is suggested by case series of severe and atypical infections as well as by reports of decreased T and natural killer (NK) lymphocyte counts. As some evidence supports a dysregulation of the CXCR4/CXCL12 chemotactic axis of HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes.
METHODS
Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating T-helper and T-cytotoxic lymphocytes (including naive, memory and activated subsets) and NK cells.
RESULTS
The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs. 1026 cells/mm, p < 0.0001), correlated with age (r = - 0.46, p = 0.005), requirement of intravenous iron or blood transfusions (median: 291 vs. 627 cells/mm, p = 0.03) and CXCR4 surface expression (r = 0.353, p = 0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs. 5.74 for CXCR4 and 3.21 vs. 4.33 for CD26, p = 0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the total T-lymphocyte population, as well as on the T-helper population and its naive subset (median on naive T-helper cells: 2.34 vs. 1.32, p = 0.0002).
CONCLUSIONS
Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.
Topics: Dipeptidyl Peptidase 4; Endothelial Cells; Humans; Killer Cells, Natural; Receptors, CXCR4; T-Lymphocytes, Helper-Inducer; Telangiectasia, Hereditary Hemorrhagic
PubMed: 34906163
DOI: 10.1186/s13023-021-02139-y -
The Indian Journal of Medical Research Jan 2023As CD4+ and CD8+ T lymphocyte numbers decline, the conventional, localized forms of tuberculosis shift to the atypical, disseminated forms. Variations in lymphocyte and...
BACKGROUND & OBJECTIVES
As CD4+ and CD8+ T lymphocyte numbers decline, the conventional, localized forms of tuberculosis shift to the atypical, disseminated forms. Variations in lymphocyte and immune cell expression levels affect how tuberculosis manifests in disseminated forms. Understanding the relationship between lymphocyte counts (CD4+ and CD8+) and pro-inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-12 and interferon, we may therefore be able to shed light on how infections spread and suggest potential biomarkers for these immune factors.
METHODS
In this study, 15 guinea pigs were infected with Mycobacterium tuberculosis (M.tb) H37Rv strain and grouped into three groups of five each for further investigation. Serum samples and bronchoalveolar lavage (BAL) fluid were examined for the expression of pro-inflammatory cytokines and T-cell subsets in guinea pigs infected with pulmonary tuberculosis and disseminated tuberculosis.
RESULTS
We found that M.tb escapes macrophages due to pro-inflammatory cytokine dysregulation. Despite the protective immunity created by T-cells and cytokines, M.tb bacilli may spread to other organs due to inflammation induced by these immune components. A high number of T-cells and stimulated cytokine production are involved in triggering inflammation after necrotic tissue develops and tuberculosis spreads.
INTERPRETATION & CONCLUSIONS
Our findings imply that increased bacilli in the spleen at the 8 wk of infection may be caused by the overexpression of CD4+ T-cell lymphocyte subsets and cytokines that generated inflammation during the 4 wk of infection. This is a pilot study with a small sample size and less assertive inference. Larger studies would be helpful to validate the results of the present investigation.
Topics: Animals; Guinea Pigs; Cytokines; Mycobacterium tuberculosis; T-Lymphocytes; Pilot Projects; Inflammation
PubMed: 37602585
DOI: 10.4103/ijmr.ijmr_2143_21 -
Frontiers in Immunology 2022Acute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response...
BACKGROUND AND OBJECTIVES
Acute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.
METHODS
Paired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19 and CD138 on liver tissues was examined by immunohistochemistry staining.
RESULTS
In this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27CD21 activated memory B cells (AM), CD27CD21 atypical memory B cells (atMBC), CD27IgDIgM(IgM memory B cells), and CD27CD38 plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27CD38plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.
CONCLUSIONS
In this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy.
Topics: Humans; Acute-On-Chronic Liver Failure; Pilot Projects; B-Lymphocytes; Plasma Cells; B-Lymphocyte Subsets; Liver Cirrhosis
PubMed: 36505417
DOI: 10.3389/fimmu.2022.1041176 -
Proceedings of the National Academy of... Jan 2023Sex-biased humoral immune responses to COVID-19 patients have been observed, but the cellular basis for this is not understood. Using single-cell proteomics by mass...
Sex-biased humoral immune responses to COVID-19 patients have been observed, but the cellular basis for this is not understood. Using single-cell proteomics by mass cytometry, we find disrupted regulation of humoral immunity in COVID-19 patients, with a sex-biased loss of circulating follicular regulatory T cells (cTfr) at a significantly greater rate in male patients. In addition, a male sex-associated cellular network of T-peripheral helper, plasma blasts, proliferating and extrafollicular/atypical CD11c memory B cells was strongly positively correlated with neutralizing antibody concentrations and negatively correlated with cTfr frequency. These results suggest that sex-specific differences to the balance of cTfr and a network of extrafollicular antibody production-associated cell types may be a key factor in the altered humoral immune responses between male and female COVID-19 patients.
Topics: Female; Humans; Male; Antibody Formation; COVID-19; Immunity, Humoral; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; B-Lymphocytes
PubMed: 36669118
DOI: 10.1073/pnas.2217902120 -
Cellular Immunology Nov 2017T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were recently shown to be critical for murine antiviral responses. While their role in human... (Review)
Review
T-bet-expressing B cells, first identified as perpetuators of autoimmunity, were recently shown to be critical for murine antiviral responses. While their role in human viral infections remains unclear, B cells expressing T-bet or demonstrating a related phenotype have been described in individuals chronically infected with HIV or HCV, suggesting these cells represent a component of human antiviral responses. In this review, we discuss the induction of T-bet in B cells following both HIV and HCV infections, the factors driving T-bet B cell expansions, T-bet's relationship to atypical memory B cells, and the consequences of T-bet induction. We propose potential antiviral roles for T-bet B cells and discuss whether this population poses any utility to the HIV and HCV immune responses.
Topics: Animals; Antibodies, Viral; B-Lymphocyte Subsets; B-Lymphocytes; HIV Infections; Hepatitis C; Humans; Immunoglobulin G; Models, Immunological; T-Box Domain Proteins
PubMed: 28739077
DOI: 10.1016/j.cellimm.2017.04.012 -
Journal of Immunology Research 2015Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease... (Review)
Review
Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (γδ) T cells are reported to have a role. γδ T cells are atypical T cells, which represent a small proportion of total lymphocytes. They have features of both innate and adaptive immunity and express characteristics of conventional T cells, natural killer cells, and myeloid antigen presenting cells. These unconventional T cells are found in the inflammatory BD lesions and have been suggested to be responsible for inducing and/or maintaining the proinflammatory environment characteristic of the disease. Over the last 20 years there has been much interest in the role of γδ T cells in BD. We review the literature and discuss the roles that γδ T cells may play in BD pathogenesis.
Topics: Animals; Antigens; Behcet Syndrome; Humans; Immunomodulation; Receptors, Antigen, T-Cell, gamma-delta; Signal Transduction; T-Lymphocyte Subsets
PubMed: 26539557
DOI: 10.1155/2015/705831