CD4 + Th cell associated cytokines and neuromyelitis optica spectrum disease / 中华实验眼科杂志

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by neuro-ophthalmic intercross and humoral immunity.Neuromyelitis optica related optic neuritis (NMO-ON) is often the initial symptom of NMOSD patients, with a high blinding rate, which brought a heavy blow to the quality of life, study, work and other aspects of patients.The discovery of aquaporin-4 immunoglobulin G (AQP4-IgG) has brought significant progress in the pathogenesis, diagnosis and treatment of NMOSD.However, AQP4-IgG is not a universal biomarker of NMOSD.The role of CD4 + T helper (Th) cell related cytokines in the pathogenesis of NMOSD has been increasingly emphasized.This paper reviewed the research results of CD4 + Th cell-related cytokines closely related to the occurrence of NMOSD in recent years, including Th17 cell-related cytokines such as interleukin-6 (IL-6), IL-17, IL-21, Th2 cell-related cytokines such as IL-4, IL-5, IL-13, IL-31, IL-33, and regulatory T cell-related cytokines, etc.to provide new insights for the pathogenesis, diagnosis and treatment strategies of NMOSD or NMO-ON.

First report of expansion of CD4+/CD28 null T-helper lymphocytes in adult patients with idiopathic autoimmune hemolytic anemia

ABSTRACT CD28 null T helper (Th) cells are rare in healthy individuals, but they are increased in various inflammatory and immune-mediated diseases. In this study, we determined the size of the CD4+/CD28 null T lymphocyte compartment in the peripheral blood of 40 autoimmune hemolytic anemia (AIHA) patients (idiopathic and secondary) and 20 healthy control subjects, using tri-color flow cytometry. The frequency and absolute count of CD4+/CD28 null T helper (Th) cells was significantly higher in idiopathic AIHA patients, compared to healthy controls (p = 0.001 and 0.001, respectively) and to patients with secondary AIHA (p = 0.04 and 0.01, respectively). The percentage of CD4+/CD28 null Th cells was also negatively correlated to the hemoglobin (Hb) level (p = 0.03). These findings demonstrate, for the first time, the expansion of this phenotypically-defined population of T lymphocytes in patients with idiopathic AIHA and indicate that it likely plays an etiological role in the development of this disease. However, establishing the use of this marker for diagnosis or monitoring treatment of such patients needs further studies.

Frequencies of regulatory subsets of CD4+ TH cells in peripheral blood in Mycobacterium Tuberculosis-Infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India

Background: Mycobacterium tuberculosis (Mtb) adapts many strategies to persist and replicate inside human tissue. One such strategy is the manipulation of CD4+ TH cells for subset interconversion to regulatory subsets. The aim of the present study is to get an insight of dynamic changes of CD4+ TH cells to regulatory subsets, CD4+ CD25+ forkhead box P3 (Foxp3)+ T-cells and CD4+ CD25+ Foxp3+ programmed death molecule-1 (Foxp3+) T-cells, in peripheral blood in Mtb-infected individuals and healthy contacts in a high-burden setting from Assam, Northeast India. Materials and Methods: A case–control study was conducted in newly diagnosed active pulmonary tuberculosis (APTBs) patients and 2 sets of controls: (i) individuals infected with latent tuberculosis infection (LTBI) and (ii) healthy close tuberculosis healthy contacts (HCs). The frequencies of different subsets of CD4+ cells with regulatory markers were measured in peripheral blood in 3 groups of study participants. Results and Observations: Frequencies of CD4+ CD25+ Foxp3+ T-cells (1.84 ± 1.40 vs. 4.32 ± 1.82 vs. 11.30 ± 3.66), CD4+ CD25+ Foxp3+ PD1+ T-cells (0.37 ± 1.28 vs. 2.99 ± 3.69 vs. 14.54 ± 5.10) and ligand (PD-L1)-positive CD4+ TH cells (0.80 ± 0.45 vs. 2.28 ± 0.95 vs. 7.13 ± 2.02) were significantly increased from HCs to LTBIs to APTB patients, respectively (P < 0.0001). No significant changes in frequencies of total CD4+ cells were observed between APTBs (29.51 ± 11.93), LTBIs (29.23 ± 8.16) and HCs (28.16 ± 9.73) whereas the mean ratios of CD4+ to CD4+ CD25+ FoxP3+ were significantly decreased from 34.34 ± 47.56 in HCs to 7.96 ± 5.8 in LTBIs to 3.12 ± 2.58 in APTBs (P < 0.0001). Significant decrease in mean ratios of CD4+ CD25+ FoxP3+ to CD4+ CD25+ FoxP3+ PD1+ were also observed from 4.97 ± 1.09 in HCs to 1.44 ± 0.49 in LTBIs to 0.78 ± 0.72 in APTBs. Conclusion: CD4+ TH cells change dynamically to regulatory subsets depending on the status of infection and a shift of response towards excessive regulatory T-cells, and PD-1/PD-L1 production may help in the development of active infection in latently infected individuals. These immunological parameters may be used, as potential biomarkers to see the changing dynamics of Mtb infection.

Effect of Yiqi Tongyang Decoction () on blood T cell subsets in patients with chronic immune thrombocytopenia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (, YTD) to explore T cell status of patients with CITP, and to defifine the mechanism of action of YTD.</p><p><b>METHODS</b>The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cells in 30 patients with CITP (22 females and 8 males) were analyzed using multiparametric flflow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers (14 males and 12 females) acted as a control. T-box expressed in T-cells (T-bet) and GATA binding protein 3 (GATA-3) mRNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction.</p><p><b>RESULTS</b>The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy (P<0.05). Th1 cell numbers and the Th1/Th2 ratio fell in the treated patients with CITP to approximate the values of the control group (P>0.05). Th17 cell numbers and the Th17/Treg ratio also decreased in the treatment group (P<0.05), but not to the levels of the controls. The number of Treg cells in the peripheral blood of patients with CITP before treatment was lower than that in the control group (P<0.05), but increased after YTD treatment P<0.05), but not to the level of controls. T-bet and GATA-3 mRNA levels in peripheral blood were initially higher in patients before treatment than controls (P<0.05), but decreased after YTD therapy (P<0.05).</p><p><b>CONCLUSIONS</b>Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cells, play important roles in the pathogenesis of CITP. YTD effificiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.</p>

Effect of protoscolex on T subsets in mice spleen cells in vitro / 中国免疫学杂志

Objective:To observe the effect of protoscolex on Th subsets and correlative cytokine in mice spleen cells in vitro.Methods:Co-culture spleen cells from BALB/c mice with protoscolices,then IL-4,IFN-γand TGF-βproduction in cell culture supernatants were analyzed by ELISA.The percentage of Th subsets were detected by Flow Cytometry analysis.Results:Secretion levels of IL-4 and TGF-βwere significantly increased in spleen cells at different time point in co-culture system with protoscolices.Ratios of Th2 and Treg cells were also significantly increased in co-culture system at different time points than the control groups.However,there was no statistical significance for ratio of Th1 cells at different time points.Conclusion:The protoscolex can increase the ratios of Th2 cells and Treg cells from spleen cells.Secretion levels of IL-4 and TGF-βwere also increased in spleen cells co-cultured with protosco-lices.The results suggest that these Th cell subsets play a role in the immune escape of the hydatid disease.

Effects of ketogenic diet on helper T cells in patients with intractable epilepsy / 中华微生物学和免疫学杂志

Objective To investigate the effects of ketogenic diet ( KD) treatment on helper T cell subsets in children with intractable epilepsy( IP) . Methods Thirty-five children with IP and eighteen age-matched healthy subjects were enrolled in this study.The percentages of CD3+CD8-IFN-γ+( Th1 ) cells, CD3+CD8-IL-17A+(Th17) cells and CD4+CD25+Foxp3+(Treg) cells were analyzed by flow cytometry.Re-al-time PCR assay was performed to evaluate the expression of T-bet, ROR-γ, IFN-γ, IL-17A and peroxi-some proliferator activated receptorγ( PPAR-γ) at mRNA level in CD4+CD25-T cells and the transcription-al levels of Foxp3, GITR, CTLA-4 and PPAR-γin CD4+CD25+T cells.The concentrations of cyclooxygen-ases-2 (COX-2) and prostaglandin F2a (PGF2α) in plasma samples were measured by enzyme-linked im-munosorbent assay.The expression of IL-17A and IFN-γin plasma samples were detected by using cytomet-ricbeadarray(CBA).Results (1)ThepercentagesofTregcellsinperipheralbloodsamplesfrompa-tients with IP were lower than those in healthy subjects (P<0.05), which were significantly increased with the treatment of KD (P<0.05).The percentages of Th17 and Th1 cells in patients with IP were significantly higher than those in healthy children (P<0.05), but were remarkably decreased with the treatment of KD (P<0.05).Patients with IP showed decreased transcriptional levels of Foxp3, GITR and CTLA-4 in CD4+CD25+T cells as compared with healthy controls, but were up-regulated with the treatment of KD.The ex-pression of transcription factors including T-bet, ROR-γ, IFN-γand IL-17A in CD4+CD25-T cells in pa-tients with IP were higher than those in healthy subjects and were down-regulated after the treatment of KD (P<0.05).(2) The expression of PPAR-γat mRNA level in CD4+CD25-T and CD4+CD25+T cells were decreased in patients with IP as compared with those in heathy controls, but were increased after the treat-ment of KD (P<0.05).Correlation analysis showed that Treg cells had a positive correlation with PPAR-γ(r=0.61, P<0.05).However, the Th1 and Th17 cells were negatively correlated with PPAR-γ[Th1 (r=-0.54, P<0.05), Th17 (r=-0.64, P<0.05) ].(3) The levels of IL-17A and IFN-γin patients with IP were higher than those in healthy controls, but were decreased with KD treatment (P<0.05).The levels of COX-2 and PGF2αin plasma samples from patients with IP were higher than those in healthy controls ( P<0.05).A negative correlation was observed between COX-2 and PPAR-γ(r=-0.571, P<0.05). Moreover, PGF2αand PPAR-γhad a negative correlation as well (r=-0.586, P<0.05).Conclusion The treatment of KD might enhance the expression of PPAR-γthrough inhibiting the products of oxidative stress such as COX-2 and PGF2α, resulting in the rebalance of Th cell subsets and reduced expression of in-flammatory cytokines.

Anti-proliferative Activity of T-bet

T-bet is a critical transcription factor that regulates differentiation of Th1 cells from CD4+ precursor cells. Since T-bet directly binds to the promoter of the IFN-gamma gene and activates its transcription, T-bet deficiency impairs IFN-gamma production in Th1 cells. Interestingly, T-bet-deficient Th cells also display substantially augmented the production of IL-2, a T cell growth factor. Exogenous expression of T-bet in T-bet deficient Th cells rescued the IFN-gamma production and suppressed IL-2 expression. IFN-gamma and IL-2 reciprocally regulate Th cell proliferation following TCR stimulation. Therefore, we examined the effect of T-bet on Th cell proliferation and found that T-bet deficiency significantly enhanced Th cell proliferation under non-skewing, Th1-skewing, and Th2-skewing conditions. By using IFN-gamma-null mice to eliminate the anti-proliferative effect of IFN-gamma, T-bet deficiency still enhanced Th cell proliferation under both Th1- and Th2-skewing conditions. Since the anti-proliferative activity of T-bet may be influenced by IL-2 suppression in Th cells, we examined whether T-bet modulates IL-2-independent cell proliferation in a non-T cell population. We demonstrated that T-bet expression induced by ecdysone treatment in human embryonic kidney (HEK) cells increased IFN-gamma promoter activity in a dose dependent manner, and sustained T-bet expression considerably decreased cell proliferation in HEK cells. Although the molecular mechanisms underlying anti-proliferative activity of T-bet remain to be elucidated, T-bet may directly suppress cell proliferation in an IFN-gamma- or an IL-2-independent manner.

Analysis of Th1-Th2-Th3 related gene expressions in the thymus of mice irradiated with different doses / 中华放射医学与防护杂志

Objective To analyze the effect of high and low dose radiation on the expressions of Th1,Th2 and Th3 /Tr1 related-genes in mice thymocytes and investigate the possible underlying molecular mechanism.Methods ICR mice were randomly divided into low-dose group (0.075 Gy),high-dose group (2.0 Gy) and sham-control group.The mouse thymus tissue was extracted at 16 hours after irradiation and the expressions of Th1-Th2-Th3 related genes were measured by PCR array.Results Eight genes were up-regulated and five genes were down-regulated after low dose radiation (0.075 Gy);while 54 genes were up-regulated and three genes were down-regulated after high dose (2.0 Gy) radiation.These genes included Th1 cell related genes,Th2 cell related genes,Th3/Tr1 cell related genes,Th1/Th2 immune response genes and transcription factor related genes.Low dose radiation induced up-regulation of Stat4 and Socs1 of genes related to the Th1 cells,and it induced down-regulation of IL-4ra,Cebpb,Gata3 and Tgfb3 associated with Th2 and Th3 cells,which lead to Sftpd genes up-regulation of Th1 immune response eventually.The high dose radiation up-regulated all of Th1,Th2 and Th3/Tr related genes and also enhanced the expressions of Cd86,IL-18,IL-10 and Irf4 genes related to Th2 immune response,but it did not alter the gene expression of Th1 immune response.Conclusions Low-dose radiation induces Th1-type immune response,while high doses radiation triggers Th2 type immune response.

The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction of articular cartilage and bone damage. The chronic treatment of RA patients causes a higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of the world’s population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb). The tuberculin skin test is used to identify individuals LTBI, but many studies have shown that this test is not suitable for RA patients. The goal of this work was to test the specific cellular immune responses to the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17 and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in RA patients candidates for tumour necrosis factor-α blocker treatment. Our results demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and HspX. Patients were followed up over two years and 14.3% developed active TB. After the development of active TB, RA patients had increased numbers of Th17 and Treg cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen assay can be used as a diagnostic test to identify LTBI RA patients.

Linfocito T y su papel en la enfermedad periodontal: Revisión de la literatura / T lymphocytes and their role in periodontal disease. Literature Review

En general es aceptado que la  condición  inmune innata y/o adaptativa puede afectar  la respuesta inmune local, incluyendo al periodonto y dentro de la progresión de la enfermedad  es crítico poder determinar la naturaleza de la respuesta inflamatoria generada por el reto microbiano antigénico subgingival. Existen controversias en la literatura a nivel mundial con respecto al papel de los linfocitos T en la enfermedad periodontal, el entendimiento de su naturaleza y la regulación  de estas células puede estar asociado a condiciones protectoras  o destructivas no estando claro aún los eventos inflamatorios o antiinflamatorios en donde la respuesta inmune celular mediada por células T  puede estar ausente o  deficiente  durante el curso de la infección periodontal. De hecho las opiniones son divididas, algunas señalan que la principal función de estas células  es la de proteger al huésped contra los microorganismos periodontopáticos, mientras que otros han demostrado su participación activa en el inicio y progresión de la enfermedad periodontal,  por esta razón la presente revisión pretende discutir  su participación dentro de la patogenia de la periodontitis  para tratar de esclarecer los mecanismos protectores y  aquellos que pueden estar relacionados con la destrucción del tejido de soporte del diente; lo cual es importante ya que nos permitiría comprender nuevos enfoques terapéuticos para esta enfermedad

In general is accepted that the innate or adaptive immunity affect the local immune response including the periodontium and in the progression of the disease is critical determinate the nature of the inflammatory response produced by the subgingival bacterial challenge. There are controversies in the literature about the role of T lymphocytes in the periodontal disease, the nature and regulation of these cells can be associated to protective o destructive conditions, but today is not clear the inflammatory or anti-inflammatory events where the cellular immune response by T cells can be absent o deficient during the course of periodontal infection. In fact the opinions about this subject are divided: some of these indicate that the main function of this cells is to protect the host against the periodontal bacteria while another had demonstrated that them participate in the beginning and progression of periodontal disease, for this reason this reviews pretend to discuss their participation in the pathogenesis of this pathology and to know the protective and destructive mechanisms relate with the destruction of periodontal tissue, this is important because they let us to understand new ways for the treatment of this disease

The immune function injury and its mechanism in drug abuser / 中国组织工程研究

Objective To explore the immune function injury and its mechanism in drug abuser.Methods The immune function changes in 50 drug abusers were compared with normal healthy populations by detection of the indexes of subgroups of Th cells, transformation rate of lymphocytes,IgA,IgM,IgG,IgE,compliment C3,C4,IL 1, IL 2,IL 6 TNF and NO.Result In peripheral blood the percentage of Th1 cell, transformation rate of lymphocyte, IgA, IgM, IgG, IgE content, compliment C4,C4, IL 1, IL 2,IL 6,and TNF levels were significantly lower than normal(P< 0.01).The value of Th1/Th2 was lower than normal as well(P< 0.05).NO content was significantly higher than normal(P< 0.001).Conclusion The mechanism of immune function injury in drug abuser might be correlative to direct injury of drugs and their inhibition effect on the thymus hypothalamus hypophysis adrenal axis.