OBJECTIVE: To explore the role of follicular helper T cell (Tfh)/ follicular regulatory T cell (Tfr) imbalance in B-cell lymphoma (BCL). METHODS: Sixteen BCL patients who were admitted to the Department of Hematology of The First People's Hospital of Yichang and 20 healthy people from December 2019 to November 2020 were enrolled and respectively divided into observation group and control group. The levels of Tfh and Tfr in peripheral blood were detected by flow cytometry. The changes of Tfh, Tfr, and Tfh/Tfr ratio were compared and the relationship between Tfh/Tfr ratio and efficacy, prognosis was analyzed. RESULTS: Compared with the healthy controls, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients increased (P<0.05, P<0.01), while levels of Tfr was decreased (P<0.01). After chemotherapy, Tfh and Tfh/Tfr ratio in peripheral blood of the BCL patients decreased significantly than before chemotherapy (P<0.01), but Tfr was no significant difference. Multivariate analysis showed that Tfh and Tfh/Tfr ratio were positively correlated with international prognostic index (IPI) score and Ann Arbor stage (r=0.626, 0.564, 0.573, 0.608, respectively), while Tfr negatively (r=－0.504, －0.542, respectively). According to the average value of Tfh/Tfr ratio at initial diagnosis, BCL patients were divided into Tfh/Tfr high ratio group and low ratio group. It was found that the complete remission (CR) rate, overall response rate (ORR), and survival time in the high ratio group were significantly lower than the low ratio group (P<0.01). CONCLUSION There is an imbalance of Tfh/Tfr ratio in peripheral blood of the BCL patients, and those with a high Tfh/Tfr ratio have lower CR, ORR and shorter survival time.
Flow Cytometry ; Humans ; Lymphoma, B-Cell ; T Follicular Helper Cells ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory

Since primary Sjögren's syndrome (pSS) is an autoummune disease of B cell hyperactivity and pathologic autoantibody response, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are suggested to be key players in pSS. We examined subsets of Tfh and Tfr cells from the blood in pSS patients, and whether these subsets represent disease activity, glandular inflammation, or autoantibody responses in pSS. Circulating Tfh and Tfr cells, along with their specific subsets, were identified from the peripheral blood of 18 pSS patients and 14 age- and sex-matched healthy controls (HCs) using flow cytometry analysis. Blood Tfr and Tfh cell ratios were increased in pSS patients compared with HCs. The CCR7(lo)PD-1(hi) subset of circulating Tfh cells was increased in pSS patients with high degree of focal lymphocytic sialadenitis; whereas circulating Tfh cells did not differ between pSS patients and HCs. The frequency of CCR7(lo)PD-1(hi) Tfh cells was significantly correlated with disease activity scores and differentiated B cells. PD-1 expression on blood Tfh and Tfr cells showed positive correlations with IL-21 in pSS. Increasing trend of blood Tfr cells was observed in pSS patients, and blood Tfr cells (particularly Th1 and Th17 subsets) represented hypergammaglobulinemia in pSS. In summary, circulating CCR7(lo)PD-1(hi) Tfh cells indicated disease activity and glandular inflammation in pSS. Circulating Tfr cells, shifted toward Th1 and Th17 subsets, indicated ongoing IgG production in pSS. Subsets of circulating Tfh or Tfr cells could be biomarkers for disease monitoring and patient stratification in pSS.
Autoantibodies ; B-Lymphocytes ; Biomarkers ; Flow Cytometry ; Humans ; Hypergammaglobulinemia ; Immunoglobulin G ; Inflammation ; Sialadenitis ; T-Lymphocyte Subsets ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory

B cells play a role in graft rejection via several mechanisms. Specifically, B cells produce high-affinity antibodies to alloantigens including allogeneic major histocompatibility complex (MHC) with the help of follicular helper T cells. B cells also function as antigen-presenting cells for alloreactive T cells, resulting in the activation of alloreactive T cells. Conversely, the frequency of regulatory B cells increases under inflammatory conditions and suppresses the rejection process. Here, the differential roles of the major B cell subpopulations (B-1, follicular B, marginal zone B, and regulatory B cells) involved in transplantation rejection are discussed together with their interaction with T cells.
Antibodies ; Antibody Diversity ; Antigen-Presenting Cells ; B-Lymphocytes* ; B-Lymphocytes, Regulatory ; Graft Rejection* ; Isoantigens ; Major Histocompatibility Complex ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer

OBJECTIVE: To explore the relation of circulating follicular helper T cell (c Tfh) changes with B cell dysfunction in MDS patients. METHODS: 20 patients diagnosed as MDS from Auguct 2015 to October 2017 were enrolled in MDS group, and 20 healthy valuntears matching in age and sex were enrolled in healthy control (HC) group. The perepheral blood in 2 groups were collected, the mononuclear cells (PBMC) from which were isolated by densily gradient contrifugation, at the same time, the serum left in isolation process was reserved for further study. The flow cytometry was used to detect the ratio of cTfh such as CD4CXCR5 T cells and its subset CD4CXCR5ICOS T cells, CD4CXCR5PD-1 T cells in PBMC, as well as the ratio of plasmablast CD19CD20CD38 B cells. The ELISA was used to detect the concentration of IgA, IgM and IgG. The differences in ratio of cTfh cells and plasmablast B cells, as well as the concentration of IgA, IgM and IgG between MDS and HC groups were compared, at the same time, the correlation of cTfh cell ratio with the plasmablast B cell ratio and the concentration of IgA, IgM and IgG in MDS patient was analyzed. RESULTS: The ratio of CD4CXCR5T, CD4CXCR5ICOST cells and CD19CD20CD38B cells and the concentration of IgA, IgM and IgG decreased in MDS patients, while the ratio of CD4CXCR5PD-1T cells increased in MDS patients. The ratio of CD4CXCR5T cells, CD4CXCR5ICOST cells positively correlated with the ratio of CD19CD20CD38B cells, as well as with the concentration of IgA, IgM and IgG in MDS patients. However, the ratio of CD4CXCR5PD-1T cells negatively correlated with the ratio of CD19CD20CD38B cells, as well as with the concentration of IgA, IgM and IgG. CONCLUSION The ratio of circulating Tfh cells and their subsets showed significant changes, that correlate with B cell dysfunction in MDS patients.
B-Lymphocytes ; Humans ; Interleukins ; Leukocytes, Mononuclear ; Myelodysplastic Syndromes ; Plasma Cells ; Receptors, CXCR5 ; T-Lymphocytes, Helper-Inducer

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation (CD)8+ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.
Germinal Center ; Immune System Diseases ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory* ; Vaccines

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORgammat. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORgammat, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.
Autoimmune Diseases ; Autoimmunity ; B-Lymphocytes ; CD40 Ligand ; Germinal Center ; Immune Tolerance ; Immunoglobulin Class Switching ; Interleukin-6 ; Interleukins ; Memory ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; Peripheral Tolerance ; Plasma Cells ; Pliability ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th17 Cells ; Transcription Factors ; Up-Regulation

Follicular helper T (TFH) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, naive T cells are differentiating into TFH cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). TFH cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and TFH cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in TFH cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and TFH cell differentiation. TFH cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of TFH cells. The miR-17-92 cluster induces Bcl-6 and TFH cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T (TFR) cells are studied as thymus-derived CXCR5+PD-1+Foxp3+ Treg cells that play a significant role in limiting the GC response. Regulation of TFH cell differentiation and the GC reaction via miRNA and TFR cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect TFH cell differentiation, and the role of TFH cells in autoimmune diseases.
Arthritis, Rheumatoid ; Autoimmune Diseases ; Autoimmunity* ; B-Lymphocytes ; CD40 Ligand ; Cell Differentiation ; Cytokines ; Germinal Center ; Immune Tolerance ; Immunity, Humoral ; Interleukin-6 ; Lupus Erythematosus, Systemic ; Memory ; MicroRNAs ; Negotiating ; Plasma Cells ; Recombination, Genetic ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer* ; T-Lymphocytes, Regulatory ; Transcription Factors

PURPOSE: To evaluate the changes of differential counts and lymphocyte subsets in cancer patients' leukocyte before and after radiotherapy. METHODS AND MATERIALS: From Dec. 1994 to May 1995, the changes of leukocyte and its subsets in 16 patients who received radiotherapy in the Dept. of Radiation Oncology of Dong-A University Hospiatal were investigated. Radiation was delivered from 2700 cGy to 6660 cGy with median dose of 5400 cGy. The results of pre- and post-radiotherapy were analyzed by paired T-test. The results of patients who received < 50 Gy and > or = 50 Gy were analyzed by wilcoxon test. RESULTS: Before and after radiotherapy, there was not any significant differences in the counts of leukocyte, granulocyte and monocyte. A remarkable decrease was noted in lymphocyte counts after radiotherapy(p=0.015). T cells, B cells and natural killer cells were also decreased in number after radiotherapy but it was not significant statistically. T helper cells and T suppressor cells were also decreased in number(p>0.05). The ratio of T helper/suppressor cell was decreased from 1.52 to 1.11 and it was significant statistically(p=0.016). The portion of T suppressor cell among all T cells was increased after radiotherapy (p=0.0195). No significant difference was observed in the analysis of leukocyte and its subsets between patients who reveived < 50 Gy and > or = 50 Gy. CONCLUSION: Radiotherapy caused remarkable decrease in lymphocyte count and its subsets. Among all lymphocyte subsets, T helper cell might be the most vulnerable to radiation, considering decreased ratio of T helper/surppressor cell count after radiotherapy.
B-Lymphocytes ; Cell Count ; Granulocytes ; Humans ; Killer Cells, Natural ; Leukocytes ; Lymphocyte Count ; Lymphocyte Subsets* ; Lymphocytes* ; Monocytes ; Radiation Oncology ; Radiotherapy* ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer

In addition to T cell-dependent (TD) Ab responses, T cells can also regulate T cell-independent (TI) B cell responses in the absence of a specific major histocompatibility complex (MHC) class II and antigenic peptide-based interaction between T and B cells. The elucidation of T cells capable of supporting TI Ab responses is important for understanding the cellular mechanism of different types of TI Ab responses. Natural killer T (NKT) cells represent 1 type of helper T cells involved in TI Ab responses and more candidate helper T cells responsible for TI Ab responses may also include γδ T cells and recently reported B-1 helper CD4⁺ T cells. Marginal zone (MZ) B and B-1 cells, 2 major innate-like B cell subsets considered to function independently of T cells, interact with innate-like T cells. Whereas MZ B and NKT cells interact mutually for a rapid response to blood-borne infection, peritoneal memory phenotype CD49d(high)CD4⁺ T cells support natural Ab secretion by B-1 cells. Here the role of innate-like T cells in the so-called TI Ab response is discussed. To accommodate the involvement of T cells in the TI Ab responses, we suggest an expanded classification of TD Ab responses that incorporate cognate and non-cognate B cell help by innate-like T cells.
Antibody Formation* ; Antigen-Antibody Reactions ; B-Lymphocyte Subsets ; B-Lymphocytes ; Classification ; Major Histocompatibility Complex ; Memory ; Natural Killer T-Cells ; Phenotype ; T-Lymphocytes* ; T-Lymphocytes, Helper-Inducer

CD4-Positive T-Lymphocytes ; Cell Differentiation ; T-Lymphocyte Subsets ; T-Lymphocytes, Regulatory