The response of CD27+CD38+ plasmablasts, CD24hiCD38hi transitional B cells, CXCR5-ICOS+PD-1+ Tph, Tph2 and Tfh2 subtypes to allergens in children with allergic asthma.

BACKGROUND: Allergic asthma is a type I allergic reaction mediated by serum Immunoglobulin E (IgE). B cell-mediated humoral immune response to allergens in the pathophysiology of allergic asthma have not been thoroughly elucidated. Peripheral helper T cells (Tph) and follicular helper T cells (Tfh) promote B cell differentiation and antibody production in inflamed tissues. OBJECTIVE: To investigate the roles of B cell subsets, Tph cell subsets and Tfh cell subsets in allergic immune responses. METHODS: Circulating B cell subsets, Tph cell subsets and Tfh cell subsets in 33 children with allergic asthma and 17 healthy children were analyzed using multicolor flow cytometry. The level of serum total IgE was also assessed. RESULTS: Our study found that CD27+CD38+ plasmablasts and CD24hiCD38hi transitional B cells increased and were correlated with serum total IgE level, CD27- naive B cells and CD24hiCD27+ B cells decreased in children with allergic asthma. CXCR5- Tph, CXCR5-ICOS+ Tph, CXCR5-ICOS+PD-1+ Tph, CXCR5+ICOS+ Tfh and CXCR5+ICOS+PD-1+ Tfh increased in children with allergic asthma. Further analysis showed increased Tph2, Tph17, Tfh2 and Tfh17 subtypes while decreased Tph1 and Tfh1 subtypes in children with allergic asthma. Most interestingly, Tph2 or Tfh2 subtypes had a positive correlation with serum total IgE level. CONCLUSION: Overall, these results provide insight into the allergens elicited B, Tph or Tfh cell response and identify heretofore unappreciated CD24hiCD38hi transitional B cells, CD24hiCD27+ B cells, CXCR5- Tph, CXCR5-ICOS+PD-1+ Tph, Tph2 subtypes and Tfh2 subtypes response to allergens.

DSF/Cu induces antitumor effect against diffuse large B-cell lymphoma through suppressing NF-κB/BCL6 pathways.

BACKGROUND: The B-cell lymphoma 6 (BCL6) oncogene is required for the survival of diffuse large B-cell lymphoma (DLBCL), which is incurable using conventional chemotherapy. Thus, it is imperative to improve the survival of patients with DLBCL. Disulfide (DSF) has been shown to have anticancer effects, but its effect on DLBCL remains unclear. METHODS: Four DLBCL cell lines (OCI-LY1, OCI-LY7, OCI-LY10 and U2932) and primary DLBCL cells from eight newly diagnosed DLBCL patients were pretreated with DSF alone or in combination with Cu. Cell morphology was observed under microscope. Flow cytometry was performed to evaluate the cell apoptosis, cell cycle, the mitochondrial membrane potential and the intracellular accumulation of reactive oxygen species (ROS). The protein expression was respectively measured by flow cytometry and western blotting. RESULTS: DSF or DSF/Cu exhibited a marked inhibitory effect on the growth of DLBCL cells, accompanied by cell cycle arrest at the G0/G1 phase. Meanwhile, DSF or DSF/Cu significantly induced DLBCL cells apoptosis. Further study revealed that DSF or DSF/Cu promoted apoptosis by inhibiting NF-κB signaling pathway. Interestingly, DSF/Cu significantly reduced BCL6 and AIP levels. In addition, DSF significantly up-regulate p53 protein in OCI-LY7 and OCI-LY10 while down-regulate p53 protein in OCI-LY1 and U2932. CONCLUSION: These results provided evidence for the anti-lymphoma effects of DSF on DLBCL and suggested that DSF has therapeutic potential to DLBCL.

Responses of CD27+ CD38+ plasmablasts, and CD24hi CD27hi and CD24hi CD38hi regulatory B cells during primary dengue virus 2 infection.

BACKGROUND: Humoral immunity is thought to play a central role in mediating the immunopathogenesis of dengue virus (DENV) infection; however, the B-cell responses elicited by primary DENV2 infection are incompletely understood. Follicular helper T cells (Tfh) are important to promote B-cell activation and differentiation. METHODS: The present study analyzed the detailed dynamic changes of circulating B-cell subsets and Tfh (cTfh) using flow cytometry to explore their responses to DENV2 infection. RESULTS: Thirty-six patients with DENV2 and 21 healthy individuals were included. The results showed that CD27+ CD38+ plasmablasts emerged after DENV2 infection, and correlated with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh, which increased after DENV2 infection, and correlated with DENV2 RNA viral loads. Significantly low levels of CD27- naïve B cells, and CD24hi CD27hi and CD24hi CD38hi regulatory B cells (Breg) were observed after DENV2 infection, which correlated negatively with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh cells. CONCLUSION: Overall, these results provide insights into the DENV2-elicited B-cell response and revealed previously unidentified CD24hi CD27hi and CD24hi CD38hi Breg responses to DENV2 infection.

Cutaneous plaque in adult T cell leukemia/lymphoma: A case report.

RATIONALE: The rarity of adult T cell leukemia/lymphoma (ATLL) in China, coupled with its clinicopathologic mimicry of primary skin disease, poses a diagnostic challenge. The method of diagnosis and mechanism of immune regulation in ATLL are discussed in the present report. PATIENT CONCERNS: A 51-year-old Chinese man was admitted to the hospital with 2-years history of systemic plaque lesions and 1-year history of left ankle joint pain. DIAGNOSES: The patient was diagnosed with ATLL based on the results of flow cytometry immunophenotype and human T-cell lymphotropic virus type 1 (HTLV-1) serology. INTERVENTIONS: The patient received 3 cycles of cyclophosphamide, epirubicin/ vinorelbine, and dexamethasone (CHOP) chemotherapy. However, he relapsed and did not respond to epirubicin, vindesine, etoposide, dexamethasone (EPOCH) chemotherapy. OUTCOMES: His family discontinued the treatment and opted for hospice care. LESSONS: Patch and plaque ATLL types exhibits a better survival rate, but atypical skin patches delays the diagnosis of ATLL and negatively affects the patient survival. Based on the present findings, we suggest that patients with petal-like nuclear lymphocytes in blood smears, a high CD4: CD8 ratio, and strong CD25 expression should undergo HTLV-1 serology testing.

Altered ratio of circulating follicular regulatory T cells and follicular helper T cells during primary EBV infection.

Follicular help T cells (Tfh) play an important role in the activation and differentiation of B cells, while follicular regulatory T cells (Tfr) control Tfh and resulting humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of Tfr contributed to the pathogenesis of infectious diseases. However, the role of Tfr in Epstein-Barr virus (EBV) infection remains lacking. Fifty-five EBV-infected infectious mononucleosis (IM) patients and 21 healthy individuals (HIs) were recruited in the study. We investigated the number of Tfr (FoxP3+CXCR5+PD-1+CD4+) and Tfh (FoxP3-CXCR5+PD-1+CD4+) of peripheral blood in IM patients at diagnosis (D0) and day 15 after diagnosis (D15) via multicolor flow cytometry. Results revealed that circulating Tfh (cTfh) and Tfr (cTfr) of IM at D0 were both increased compared to HIs, and cTfr began to decline and return to normal at D15, while cTfh was still higher than those of HIs. More interestingly, the cTfr/cTfh ratio of IM at D0 and D15 was lower than that of HIs, suggesting that the balance between cTfh and cTfr was disturbed during primary EBV infection. Correlation analysis showed a positive correlation between cTfr with CD19+IgD+CD27- naive B cells, CD19+IgD-CD27hi plasmablasts or CD19+CD24hiCD27hi B cells. Moreover, both cTfr and the cTfr/cTfh ratio of IM at D0 were negatively correlated with EBV DNA virus load. These results indicate that an imbalance of cTfr and cTfh cells may be involved in the immunopathogenesis of EBV-infected IM patients and may provide novel strategies for controlling EBV-related disease.

Protective role of follicular CXCR5+CD8+ T cells against dengue virus 2 infection.

Follicular CXCR5+CD8+ T cells have antiviral effects in chronic virus infection, but the roles of these cells during dengue virus 2 (DENV2) infection remain poorly understood. OBJECTIVE: This study was conducted to analyzed in detail the dynamic changes and functional properties of circulating follicular CXCR5+CD8+ T cells to explore their effects on DENV2 infection. METHODS: Circulating follicular CXCR5+CD8+ T cells and cytokines were analyzed by flow cytometry in DENV2 patients at difference days after DENV2 infection. CD8+ T cells were isolated and purified from DENV2 patients, then were stimulated with NS1 peptides and TCR stimulant. After cultivation, multiple parameters were tested. RESULTS: (1) CXCR5+CD8+ T cells emerged after DENV2 infection, with high PD-1 expression, and were correlated with the reduction in DENV2 RNA viral loads. (2) PD-1+CXCR5+CD8+ T cells were negatively associated with disease progression. (3) Serum IFN-γ, IL-6 and IL-10 levels were increased late in the course of DENV2 infection. (4) CXCR5+CD8+ T cells from DENV2 patients exhibited increased cytotoxicity and IFN-γ and IL-10 secretion. CONCLUSION: CXCR5+CD8+ T cells could play a protective role in dengue pathogenesis and may be a novel strategy for controlling DENV2 infection and vaccine development.

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen-DR- cell differentiation in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) represents one of the most common and aggressive cancers worldwide, as it typically displays irreversible progression and poor prognosis. Interaction between programmed death 1 (PD-1) and its ligand, PD-L1, plays important roles in tumor immunology. Follicular helper T (Tfh) cells have characteristically high PD-1 expression; thus, in the present study, we investigated the role of circulating Tfh cells and their correlation with disease-free survival after tumor resection in NSCLC. We found significantly higher number of Tfh cells but lower serum interleukin (IL)-21 levels in NSCLC patients, especially in those with advanced stage (III and IV), indicating that the function of Tfh cells to produce IL-21 was impaired. Further analysis showed that the increase in Tfh cells was attributable to an expansion of the PD-1+ -Tfh2 and PD-1+ -Tfh17 subtypes. Functional analysis showed that Tfh cells from NSCLC patients induced the differentiation of regulatory B cells and CD14+ human leukocyte antigen (HLA)-DR- cells. Interestingly, the number of Tfh1 subtypes in NSCLC patients was negatively correlated with disease-free survival after tumor resection. In short, the high number and abnormal function of Tfh cells could cause further immunosuppression and lead to tumor development in NSCLC. Rescuing Tfh functions therefore represents a potential therapeutic strategy in NSCLC.

Elevated levels of follicular T helper cells and their association with therapeutic effects in patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression. Our findings revealed the expansion of circulating CD4+CXCR5+, CD4+ICOS+, CD4+PD-1+ and CD4+CXCR5+ICOS+PD-1+ (Tfh) cells but lower serum IL-21 levels and CD4+ T cell polarization not only to Tfh2 subtypes but also to Tfh17 subtypes in patients with CLL at pretreatment compared to patients with monoclonal B cell lymphocytosis (MBL) and healthy individuals, especially in those with advanced stage, which indicate these Tfh cells could be employed as a novel indicator for disease progression. Moreover, we observed significant correlations of Tfh17 and immunoglobulin heavy chain variable region (IGHV) mutation. Importantly, significantly decreased CD4+ICOS+, CD4+PD-1+ and Tfh cells were found after effective treatments, whereas a significantly high CD4+ICOS+, CD4+PD-1+ and Tfh cells were still found in those with progressive disease after treatments, suggesting that circulating CD4+ICOS+, CD4+PD-1+, Tfh cells could predict therapeutic effects.

RETRACTED: Aberrant frequency of IL-10-producing B cells and its association with Treg and MDSC cells in Non Small Cell Lung Carcinoma patients.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The Editor-in-Chief has retracted this article due to serious problems with copied and re-labeled images in several figures. Specifically, the problematic items are the HC and Stage I samples in figure 1D (IL-10/CD19) and figure 2B (CD127/CD25), in which the flow dot plots outside of the boxes are identical. This strongly suggests that the data was manipulated. The authors were unable to provide the raw data files to prove otherwise. This makes the overall conclusions of the paper unreliable and violates our ethical publishing policies. The corresponding author, Liannv Qiu takes full responsibility and apologizes to all co-authors in this article, and the editors and readership of Human Immunology for any negative impact this may have on the journal.