OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR⁺/IG^-, 26.3% (5/19) TCR⁺/IG⁺, 10.5% (2/19) were TCR^－/IG^－, and 5.3% (1/19) TCR^－/IG⁺. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR^－/IG^－, 1 case with TCR^－/IG⁺, and 1 case with TCR⁺/IG⁺; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR^－/IG^－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.
Humans ; Epstein-Barr Virus Infections/genetics* ; Herpesvirus 4, Human/genetics* ; T-Lymphocytes, Helper-Inducer/pathology* ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Receptors, Antigen, T-Cell

OBJECTIVE: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL). METHODS: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed. RESULTS: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(r_s=-0.32，r_s=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (r_s=0.79，r_s=0.54，r_s=0.58； r_s=0.72，r_s=0.63，r_s=0.45), but not with WBC, CD4⁺ T cells and CD8⁺T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (r_s=0.53). CONCLUSION Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Interleukin-9 ; Clinical Relevance ; T-Lymphocytes, Helper-Inducer/pathology* ; Cytokines

Immunoglobulin G4-related disease (IgG4-RD) is an emerging immune-mediated fibro-inflammatory disorder which can involve any organ. The main characteristics of IgG4-RD are increased serum IgG4 concentration, abundant IgG4+ plasma cells in affected tissues, and painless swollen organs often without general symptoms. Typical pathology features of IgG4-RD are lymphoplasmacytic infiltration, dense storiform fibrosis, and obliterative pheblitis. The pathogenesis of IgG4-RD remains elusive, but involvement of excess production of type 2 T helper cells, regulatory T-cell cytokines, and B-cell activating factor in the development of IgG4-RD has been suggested. Diagnosis of IgG4-RD can be made on the basis of serological, imaging, particularly histopathological findings. Glucocorticoid is the first-line therapy for patients with multiple organ dysfunction and clinical symptoms. Drugs such as azathioprine, mycophenolate mofetil, methotrexate, and cyclophosphamide can be used as steroid-sparing agents. Rituximab is reported to be an effective therapy for treatment of IgG4-RD, even without concomitant glucocorticoid therapy. This review summarizes current concepts on pathophysiology, clinical manifestations, and treatment of IgG4-RD.
Azathioprine ; B-Cell Activating Factor ; Cyclophosphamide ; Cytokines ; Diagnosis ; Fibrosis ; Humans ; Immunoglobulin G ; Immunoglobulins* ; Methotrexate ; Pathology ; Plasma Cells ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Rituximab

Biomarkers, Tumor ; metabolism ; Humans ; Immunoblastic Lymphadenopathy ; metabolism ; pathology ; Lymphoma ; genetics ; metabolism ; pathology ; Lymphoma, Follicular ; genetics ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; genetics ; metabolism ; pathology ; Signal Transduction ; Skin Neoplasms ; metabolism ; pathology ; T-Lymphocytes, Helper-Inducer ; metabolism ; pathology

Antigen Presentation ; Apoptosis ; Hepatitis C ; Humans ; Lichen Planus, Oral ; etiology ; genetics ; pathology ; virology ; Polymorphism, Single Nucleotide ; T-Lymphocytes, Cytotoxic ; pathology ; T-Lymphocytes, Helper-Inducer ; pathology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo reveal the different molecular mechanisms between Chinese drugs for activating blood (CDAB) and Chinese drugs for nourishing qi and activating blood (CDNQAB) in the metastasis process of Lewis lung carcinoma, thus providing experimental reliance for Chinese drugs to reverse immune escape.

METHODSThe inhibition rate of lung metastasis was observed in each group. The dynamic percentage and ratio changes of Th17 and Treg cells in spleen CD4+ T lymphocytes were detected using flow cytometry. The dynamic levels of IL-17, IL-23, and gamma interferon (IFN-gamma) in the culture supernatant of CD4+ T lymphocytes were detected by ELISA. The dynamic mRNA expressions of Foxp3 and RORgammat in CD4+ T lymphocytes were detected by RT-PCR.

RESULTSCDNQAB (sapanwood +astragalus) showed better lung metastasis inhibiting rate than CDAB (sapanwood alone) (P<0.05), similar to the effects of cyclophosphamide (P>0.05). Except the CDNQAB group, spleen Th17 and Treg cells showed a rising tendency in mice of each tumor-bearing group. The effectors of Th17 and Treg cells (IL-17, IL-23, and IFN-gamma) and key transcription molecules of Th17 and Treg cells (RORgammat and Foxp3) showed dynamic changes corresponding to Th17 and Treg cells.

CONCLUSIONSThe immune inflammatory reactions of CDNQAB (sapanwood +astragalus) were superior to those of CDAB (sapanwood alone) and of cyclophosphamide during the process of inhibiting tumor immunotolerance and of the formation of tumor. All drugs showed certain inhibition on the mechanisms for neoplasm metastasis. But CD-NQAB was superior to CDAB and chemotherapeutics.

Animals ; Carcinoma, Lewis Lung ; drug therapy ; immunology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; immunology ; Interleukin-17 ; immunology ; Interleukin-23 ; immunology ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; T-Lymphocytes, Helper-Inducer ; immunology ; T-Lymphocytes, Regulatory ; immunology

Hashimoto's thyroiditis (HT) is a autoimmune disease that is highly incident year by year. Its clinical manifestations are alternative hyperthyroidism or hypothyroidism, relatively high Th1, excessively low Th2 and constantly increasing TGAb and TMAB. Currently, the disease is still difficult to be cured, and instable thyroid function makes it harder to be treated. Therefore, this essay makes a summary analysis on domestic and foreign studies on HT's pathogenesis, clinical manifestations and treatment, resulting that pure supplement or immunosuppressive therapy is hard to achieve notable efficacy, while existing traditional Chinese medicines could only mitigate clinical symposiums but did not reduce inflammation. Therefore, to look for methods and drugs for adjusting immunity imbalance by decreasing Th1 cell factors and increasing Th2 cell factors is significant to HT treatment to some extent.
Animals ; Autoantibodies ; immunology ; Female ; Humans ; T-Lymphocytes, Helper-Inducer ; immunology ; Thyroiditis, Autoimmune ; drug therapy ; immunology ; pathology

This study was aimed to investigate the T cell (helper T cells) immune status in ITP patients and its relation with therapeutic response. 20 de novo ITP patients were enrolled (8 males, 12 females) with a median age of 41 (20 to 81). Real-time RT-PCR method was used to measure the gene expression of Th cells including T-bet, IFN-γ, GATA-3, TGF-β, Foxp3, IL-2, IL-4 in PBMNC of ITP patients before and after conventional dose of prednisone therapy [1 mg/(kg·d)] and in PBMNC of 20 normal controls. The results showed that T-bet, IFN-γ and IL-2 were significantly over-expressed in PBMNC of ITP patients before treatment compared with that in normal controls (p < 0.01), and compared with that before treatment, T-bet, IFN-γ, and IL-2 were markedly down-regulated in ITP patients after treatment. Before treatment, the expressions of Foxp3, TGF-β, GATA3 and IL-4 in ITP patients did not show difference from normal controls, while after treatment Foxp3 were more up-regulated than that before treatment (p < 0.05). After treatment, TGF-β expression showed a different pattern between old and young patients. TGF-β expression was down-regulated (p < 0.05) among ITP patients younger than 60, while up-regulated in older patients. It is concluded that there is an imbalance of Th1/Th2/Treg cytokines in ITP patients, which can be reversed by glucocorticoid treatment. The conventional dose of glucocorticoid may be regarded as effective therapy for de novo ITP patients, it may correlate with improvement of imbalance between Th1/The2/Treg cytokines.
Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Forkhead Transcription Factors ; metabolism ; Gene Expression ; Gene Expression Regulation ; Glucocorticoids ; therapeutic use ; Humans ; Interferon-gamma ; metabolism ; Interleukin-2 ; metabolism ; Male ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; metabolism ; pathology ; T-Box Domain Proteins ; metabolism ; T-Lymphocytes, Helper-Inducer ; metabolism ; Transforming Growth Factor beta ; metabolism ; Young Adult

It was long believed that platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies in idiopathic thrombocytopenic purpura. However, humoral mechanisms cannot account for all observations made in this disorder, and it is increasingly evident that cellular mechanisms contribute to platelet destruction. In this review the tolerance of T cell, abnormality of T cell apoptosis, abnormal activation of T cells, T cell subtype and its function changes, and T cell-mediated cytotoxicity were summarized.
Apoptosis ; immunology ; Autoantibodies ; immunology ; Humans ; Immune Tolerance ; Immunity, Cellular ; immunology ; Purpura, Thrombocytopenic, Idiopathic ; immunology ; T-Lymphocyte Subsets ; immunology ; T-Lymphocytes ; immunology ; pathology ; T-Lymphocytes, Cytotoxic ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology

OBJECTIVETo evaluate the quantitative and functional changes of T helper (Th) cell subsets in the bone marrow of severe aplastic anemia (SAA) patients and the relationship between these changes and the patients hematopoietic function.

METHODSBy FACS, the quantity and ratio of Th1 and Th2 cells, the percentage of CD3(+)CD8(+) cells in the bone marrow were detected in 24 patients with SAA at active phase, 15 patients with SAA at recovery phase, and 16 normal controls. By radioimmunoassay, the serum levels of TNF-alpha, or IL-4 in 20 SAA patients at active phase, 12 at recovery phase and 16 normal controls were measured. The relationships between CD3(+)CD8(+) cells, TNF-alpha and Ret, ANC; and between Th1 cells and CD3(+)CD8(+) cells, TNF-alpha or Ret, ANC; between IL-4, balance of Th1/Th2 and Ret, ANC were evaluated.

RESULTSThe percentages of Th1 and Th2 cells, and ratio of Th1/Th2 in bone marrow of SAA patients at active phase were (4.87 +/- 2.64)%, (0.41 +/- 0.26)% and 21.22 +/- 5.07, respectively, being higher than those of normal controls [(0.42 +/- 0.30)% (P < 0.01), (0.24 +/- 0.17)% (P < 0.05) and (1.57 +/- 0.93) (P < 0.01), respectively] and all of them reduced to normal levels of SAA at recovery phase (P > 0.05). The percentage of CD3(+)CD8(+) cells significantly decreased from (32.32 +/- 8.69)% at active phase to (13.76 +/- 2.96)% at recovery phase (P < 0.01). The serum levels of TNF-alpha and IL-4 at active phase was (4.29 +/- 3.15) microg/L and (1.24 +/- 0.73) microg/L, respectively, being higher than those of normal controls (1.21 +/- 1.16) microg/L, (1.18 +/- 0.97) microg/L, but only the difference of TNF-alpha was statistically significant (P < 0.01). In recovery SAA patients, the serum levels of TNF-alpha significantly decreased to (1.46 +/- 1.41) microg/L (P < 0.01), and the levels of IL-4 increased markedly to (3.05 +/- 1.94) microg/L. The CD3(+)CD8(+) cells and TNF-alpha of patients negatively correlated with Ret (P < 0.05; P < 0.05) and ANC (P < 0.05; P < 0.05), Th1 cells correlated with CD3(+)CD8(+) cells and TNF-alpha positively (P < 0.01; P < 0.05), the Ret and ANC negatively (P < 0.01; P < 0.01), IL-4 and the balance of Th1/Th2 positively correlated with Ret and ANC (P < 0.05, P < 0.01; P < 0.01, P < 0.01).

CONCLUSIONThe bone marrow failure in SAA might be caused not only by the increase of Th1 cells, Th1 type effector cells and cytokines, but also by insufficient compensation of Th2 cells and Th2 type cytokines, which shifted the balance of Th1/Th2 favorable to Th1.

Adolescent ; Adult ; Anemia, Aplastic ; blood ; pathology ; physiopathology ; Bone Marrow ; metabolism ; pathology ; CD3 Complex ; blood ; CD8 Antigens ; blood ; Child ; Female ; Hematopoietic System ; metabolism ; pathology ; physiopathology ; Humans ; Interleukin-4 ; blood ; Male ; Middle Aged ; Radioimmunoassay ; T-Lymphocytes, Helper-Inducer ; metabolism ; pathology ; Th1 Cells ; metabolism ; pathology ; Th2 Cells ; metabolism ; pathology ; Tumor Necrosis Factor-alpha ; blood ; Young Adult