1.Circulating CCR7(lo)PD-1(hi) Follicular Helper T Cells Indicate Disease Activity and Glandular Inflammation in Patients with Primary Sjögren's Syndrome
Ji Won KIM ; Jaeseon LEE ; Seung Min HONG ; Jennifer LEE ; Mi La CHO ; Sung Hwan PARK
Immune Network 2019;19(4):e26-
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
2.Analysis of Lymphocyte Subsets in Peripheral Blood after Radiotherapy.
Jung Man KIM ; Hyung Sik LEE ; Won Joo HUR ; Jeung Kee KIM ; Young Min CHOI
Journal of the Korean Society for Therapeutic Radiology 1996;14(3):229-236
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
4.Expansion and Sub-Classification of T Cell-Dependent Antibody Responses to Encompass the Role of Innate-Like T Cells in Antibody Responses.
Immune Network 2018;18(5):e34-
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*
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Antigen-Antibody Reactions
;
B-Lymphocyte Subsets
;
B-Lymphocytes
;
Classification
;
Major Histocompatibility Complex
;
Memory
;
Natural Killer T-Cells
;
Phenotype
;
T-Lymphocytes*
;
T-Lymphocytes, Helper-Inducer
5.Clinical Significance of Tfh/Tfr Cell Imbalance in Patients with B-Cell Lymphoma.
Jing ZHENG ; Zhu ZHANG ; Yong-Hong CHEN ; Yao XIAO ; Rong SHEN ; Lin WANG ; Ping ZHANG ; Qian-Yun YANG ; Chun FENG ; Kai-Bo GAO
Journal of Experimental Hematology 2021;29(5):1510-1516
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
6.The Role of B Cells in Transplantation Rejection.
The Journal of the Korean Society for Transplantation 2018;32(1):1-6
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
7.Relation of Circulating Follicular Helper T Cell Changes with B Cell Dysfunction in MDS Patients.
Hui LIU ; Hui-Qin CAO ; Jian-Qiang ZHAO
Journal of Experimental Hematology 2019;27(4):1196-1200
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
8.B-lymphocyte, T-lymphocyte and Subsets in Unexplained Recurrent Spontaneous Abortion.
Korean Journal of Obstetrics and Gynecology 1997;40(6):1157-1161
The depressed cell-mediated immunity in pregnant women may play an important role inthe protection of the fetus from rejection by the mother. In this of view, many studieshave been performed to evaluated of lymphocyte subsets in recurrent spontaneous abortionwomen. However, because of the discordance in published data, auther have reevaluatedperipheral blood T-lymphocyte, B-lymphocyte and subsets defined by monoclonal antibodieswith immunobead method for 37 recurrent spontaneous abortion women and 30 normal healthywomen.The results were as follows. No significant difference was observed in the componentratio of the B cell. The component ratio of T lymphocyte in study group(70.5+/-10.1%) wassignificantly decreased in control group(79.7+/-3.1%)(p < 0.001). The component ratio of Nullcell in study group(19.0+/-10.1%) was higher than control group(9.4+/-2.6%)(p < 0.001). In thecomponent ratio of T4 cell, no statistically difference were observed in both groups. In thecomponent ratio of T8 cell, study group(28.4+/-9.5%) was significantly lower than controlgroup(38.4+/-3.2%)(p < 0.001). T4/ T8 ratio in the study group(1.58+/-0.70%)was significantly higher than control group(1.09+/-0.14%)(p < 0.001).In the component ratio of T/B cell, no statistically differences were observed.In conclusion, decreased T8 cell component ratio and increased T4/T8 component ratio may be play an important role in recurrent spontaneous abortion.
Abortion, Spontaneous*
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B-Lymphocytes*
;
CD4-Positive T-Lymphocytes
;
CD8-Positive T-Lymphocytes
;
Female
;
Fetus
;
Humans
;
Immunity, Cellular
;
Lymphocyte Subsets
;
Lymphocytes
;
Mothers
;
Pregnancy
;
Pregnant Women
;
T-Lymphocytes*
9.Immunoregulatory Effect of Mesima (R) as an Immunotherapeutic Agent in Stage III Gastric Cancer Patients after Radical Gastrectomy.
Jin Pok KIM ; Keon Young LEE ; Hang Jong YU ; Han Kwang YANG
Journal of the Korean Cancer Association 1997;29(3):383-390
PURPOSE: The effectiveness of adjuvant immunotherapy with Mesima (R) in advanced adenocarcinoma of the stomach was evaluated. MATERIALS AND METHODS: 45 patients with stage III gastric cancer after radical gastrectomy were divided into three groups at random. The first group received Mesima. The second group received OK-432 and the third group received no immunotherapeutic agent at all. All three groups received adjuvant chemotherapy using 5-FU and mitomycin-C protocol. The numbers of total T lymphocytes were checked along with the T4 and T8 subpopulation and B lymphocytes and natural killer (NK) cells preoperatively and 9 days, 3 months and 7 months postoperatively. The delayed-type cutaneous hypersensitivity were also checked preoperatively and 3 months and 7months postoperatively. RESULTS: All three groups showed initial decrease in the total T lymphocyte count and T4 lymphocyte count at 9 days postoperatively, which showed gradual increase over the 7 months postoperative period. The Mesima (R)-treated group and OK-432-treated group showed significantly better recovery rate at 7 months postoperatively than the control group. The number of T8 lymphocytes and NK cells also showed initial decrease and later recovery, but there was no significant difference between groups. The number of B lymphocytes showed gradual decrease over 7 months in the Mesima (R)-treated group and the control group, and initial decrease with later increase in the OK-432-treated group, again with no significant difference. The average numbers of positive antigens on delayed cutaneous hypersensitivity test were decreased initially with gradual increase, but there was no significant difference between groups. CONCLUSION: Mesima (R) can be considered as a candidate for safe and effective immunotherapeutic agent in patients with gastric cancer, but the actual benefit in increasing patient survival should be determined through a long term follow-up study.
Adenocarcinoma
;
B-Lymphocytes
;
CD4 Lymphocyte Count
;
CD8-Positive T-Lymphocytes
;
Chemotherapy, Adjuvant
;
Fluorouracil
;
Follow-Up Studies
;
Gastrectomy*
;
Humans
;
Hypersensitivity
;
Immunotherapy
;
Killer Cells, Natural
;
Lymphocyte Count
;
Mitomycin
;
Picibanil
;
Postoperative Period
;
Stomach
;
Stomach Neoplasms*
;
T-Lymphocytes
10.A Case of Idiopathic CD4 + T Lymphocytopenia Associated with Kaposi's Sarcoma.
Hyun Tae LEE ; Ho Sun JANG ; Kyung Sool KWON ; Tae Ahn CHUNG
Korean Journal of Dermatology 1997;35(1):191-195
Idiopathic CD4+ T lymphocytopenia (ICL) is a new disease entity characterized by depletion of helper T cells apparently without any evidence of HIV infection. We report a case of ICL associated with Kaposis sarcoma (KS) and pneumocystis carinii pneumonia (PCP) in a 34-year old woman. She developed violaceous, protruding masses on scalp, back, both extremities, palms, soles, left. first toe and peritonsillar region for 2 months. These lesions were confirmed as KS by histopathologic findings. Chest X-ray and HRCT findings represented PCP and KS. Absolute deficiency of CD4+ T cell was detected in the count of T cell subsets. Serologic tests for HIV-1, 2 and HTLV I, -II were negative. And she was absent any defined immunodeficiency or therapy associated with decreased levels of CD4+ T cells. By CDC criteria, a diagnosis of ICL was made. Because of aggravation of PCP and lung involuement of KS, she died at 22nd day after admission.
Adult
;
Centers for Disease Control and Prevention (U.S.)
;
Diagnosis
;
Extremities
;
Female
;
HIV Infections
;
HIV-1
;
Humans
;
Lung
;
Lymphopenia*
;
Pneumonia, Pneumocystis
;
Sarcoma, Kaposi*
;
Scalp
;
Serologic Tests
;
T-Lymphocyte Subsets
;
T-Lymphocytes
;
T-Lymphocytes, Helper-Inducer
;
T-Lymphocytopenia, Idiopathic CD4-Positive
;
Thorax
;
Toes