Effects of propofol anesthesia and sevoflurane anesthesia on the differentiation of human T-helper cells during surgery

Background Surgical stress causes a helper T-cell type 2 （Th2）-dominant status and disturbs the Th1/Th2 cytokine balance. Anesthesia can suppress the stress response to surgery, therefore it may inhibit the imbalance in the Th1/Th2 ratio. In this study, we assessed if propofol anesthesia and sevoflurane anesthesia influence the Th1/Th2 cytokine balance, and which anesthesia method better attenuates this ratio.Methods Twenty-eight patients with an American Society of Anesthesiologists （ASA） physical status of I undergoing laparoscopic cholecystectomy were selected. They were randomly allocated into two groups of 14. Group 1 received propofol anesthesia by a target-controlled-infusion （TCI） pump and group 2 received sevoflurane anesthesia.Non-invasive blood pressure, heart rate, and end-expiration CO2 partial pressure were monitored during anesthesia. The depth of anesthesia was measured using the bispectral index （BIS）, and maintained between 50 and 60. During surgery we adjusted the doses of propofol and sevoflurane according to the BIS. Samples of peripheral blood were taken before the induction of anesthesia （T1）, after the induction of anesthesia （T2）, at the beginning of surgery （T3）, at the end of surgery （T4） and on the first day after surgery （D1）. Blood samples were analyzed to give the Th1/Th2 ratio and plasma level of cortisol.Results Non-invasive blood pressure, heart rate and end-expiration CO2 partial pressure were not notably different in the two groups. At T4, the percentage of T1 cells was higher in group 1 and had statistical significance （P 〈0.05）. The percentage of T2 cells was not significantly different in the two groups. At T4, the difference in the Th1/Th2 ratio was significantly different. At T3, T4, and D1, the plasma level of cortisol was lower in group 1（P 〈0.05）.Conclusion Compared with sevoflurane, propofol can preferably promote Th cells to differentiate into Th1 cells and inhibit surgical stress. Propofol may therefore be immunoprotective for such patients.

Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

The interactions of CD4^(+)T cells and B cells are fundamental for the generation of protective antibody responses,as well as for the development of harmful autoimmune diseases.Recent studies of human tissues and blood samples have established a new subset of CD4^(+)B helper T cells named peripheral helper T(Tph)cells.Unlike T follicular helper(Tfh)cells,which interact with B cells within lymphoid organs,Tph cells provide help to B cells within inflamed tissues.Tph cells share many B helper-associated functions with Tfh cells and induce B cell differentiation toward antibody-producing cells.The differentiation mechanism is also partly shared between Tph and Tfh cells in humans,and both Tfh and Tph cells can be found within the same tissues,including cancer tissues.However,Tph cells display features distinct from those of Tfh cells,such as the expression of chemokine receptors associated with Tph cell localization within inflamed tissues and a low Bd-6/Blimp1 ratio.Unlike that of Tfh cells,current evidence shows that the target of Tph cells is limited to memory B cells.In this review,we first summarize recent findings on human Tph cells and discuss how Tph and Tfh cells play shared and distinct roles in human diseases.

New insights into the immunopathogenesis of systemic lupus erythematosus： the role of T follicular helper cells

Objective To review the development of T follicular helper （TFH） cells and their role in systemic lupus erythematosus （SLE） pathogenesis, the effect of dendritic cells （DCs） on TFH cells in SLE, as well as the potential use of TFH cells as a new therapeutic target in clinical practice. Data sources The data used in this review were retrieved mainly from the PubMed database （1989-2013）. The terms used in the literature search were ＂T follicular helper cells,＂ ＂systemic lupus erythematosus,＂ and ＂dendritic cells.＂ Study selection Relevant publications about the TFH cells development, the interaction between the TFH cells and the DCs, and the clinical applications of TFH cells were identified, retrieved, and reviewed. Results TFH cells, a novel distinct CD4＋ T cell subset, are specialized in providing help to B cells in the formation of germinal centers （GCs） and long-term protective humoral immune responses. The development of TFH cells from naive CD4＋ T cell is a multistep process. As the pivot of immunoregulation, DCs are indispensable for TFH cells generation. In addition to receptor-ligand interactions between TFH cells and DCs, the cytokines secreted by DCs are also necessary for TFH cell generation. TFH cell dysregulation has been implicated in the development of SLE. More evidence from animal models of SLE and SLE patients suggests that TFH cells are necessary for pathogenic autoantibody production. Therefore, therapeutically targeting TFH cells can be a promising approach to treat antibody-mediated autoimmune diseases including SLE. Conclusion TFH cells play a critical role in the pathogenesis of SLE, making them attractive therapeutic targets in clinical practice.

Impaired balance of T helper 17/T regulatory cells in carbon tetrachloride-induced liver fibrosis in mice

AIM: To investigate the effect of T helper (Th) 17/T regulatory (Treg) cells on hepatic fibrosis in mice and its possible mechanism.

The role of the T follicular helper cells in allergic disease

T follicular helper （Tfh） cells were discovered just over a decade ago as germinal centre T cells that help B cells make antibodies. Included in this role is affinity maturation and isotype switching. It is here that their functions become less clear. Tfh cells principally produce IL-21 which inhibits class switching to IgE. Recent studies have questioned whether the germinal centre is the main site of IgE class switching or IgE affinity maturation. In this review, I will examine the evidence that these cells are responsible for regulating IgE class switching and the relationship between Tfh cells and T helper 2 （Th2） effector cells.

Understanding the development and function of T follicular helper cells

A fundamental function of T helper(Th)cells is to regulate B-cell proliferation and immunoglobulin class switching,especially in the germinal centers.Th1 and Th2 lineages of CD41 T cells have long been considered to play an essential role in helping B cells by promoting the production immunoglobulin G2a(IgG2a)and IgG1/IgE,respectively.Recently,it has become clear that a subset CD41 T cells,named T follicular helper(Tfh)cells,is critical to B-cell response induction.In this review,we summarize the latest advances in our understanding of the regulation of Tfh cell differentiation,the relationship of Tfh cells to other CD41 T-cell lineages,and the role of Tfh cells in health and disease.

BCR–ABL-specific CD4^(+) T-helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells

The advent of tyrosine kinase inhibitor(TKI)therapy markedly improved the outcome of patients with chronic-phase chronic myeloid leukemia(CML).However,the poor prognosis of patients with advanced-phase CML and the lifelong dependency on TKIs are remaining challenges;therefore,an effective therapeutic has been sought.The BCR–ABL p210 fusion protein’s junction region represents a leukemia-specific neoantigen and is thus an attractive target for antigen-specific T-cell immunotherapy.BCR–ABL p210 fusion-region-specific CD4+T-helper(Th)cells possess antileukemic potential,but their function remains unclear.In this study,we established a BCR–ABL p210 b3a2 fusion-region-specific CD4+Th-cell clone(b3a2-specific Th clone)and examined its dendritic cell(DC)-mediated antileukemic potential.The b3a2-specific Th clone recognized the b3a2 peptide in the context of HLA-DRB1*09:01 and exhibited a Th1 profile.Activation of this clone through T-cell antigen receptor stimulation triggered DC maturation,as indicated by upregulated production of CD86 and IL-12p70 by DCs,which depended on CD40 ligation by CD40L expressed on b3a2-specific Th cells.Moreover,in the presence of HLA-A*24:02-restricted Wilms tumor 1(WT1)235–243 peptide,DCs conditioned by b3a2-specific Th cells efficiently stimulated the primary expansion of WTI-specific cytotoxic T lymphocytes(CTLs).The expanded CTLs were cytotoxic toward WT1235–243-peptide-loaded HLA-A*24:02-positive cell lines and exerted a potent antileukemic effect in vivo.However,the b3a2-specific Th-clone-mediated antileukemic CTL responses were strongly inhibited by both TKIs and interferon-α.Our findings indicate a crucial role of b3a2-specific Th cells in leukemia antigen-specific CTL-mediated immunity and provide an experimental basis for establishing novel CML immunotherapies.

Effect of pretreatment with different concertrations of morphine, fentanyl and tramadol on the differentiation of human helper T cells in vitro

Objective： To investigate and compare the .effects of different concentrations of morphine, fentanyl and tramadol on the differentiation of human adult helper T cells in vitro. Methods： Twenty out-patients without immune disease were selected and their peripheral blood was collected. Then the Whole blood of peripheral blood mononuclear cells （PBMCs） were pretreated with different concentration of morphine, fentanyl and tramadol for 24 h. The level of CD4^＋ IFN-γ^＋ IL-2^＋/CD4^＋ IL-4^＋ IL-10^＋ was analyzed by three-color flow cytometry, and the CD4^＋ CCR5^＋ and CD4^＋ CCR3 ^＋ cells were counted to observe the imbalance of Th2/Th2. Results： The number of Th2 increased significantly and the ratio of Th2/Th2 decreased dramatically compared with the control group, and there was a dose-dependent fashion in all drugs. Conclusion： Morphine, fentanyl and tramadol can direct Th0 cells toward Th2 differentiation, especially morphine and fentanyl.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Advances in the role of follicular T helper cells in graft versus host diseases

Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis.Cells producing the cytokine,interleukin(IL)-21 are crucial players involved in injured tissues in GVHD patients.Besides T helper 17 cells,follicular T helper(Tfh)cells are a new source of IL-21 and play a vital role in GVHD pathogenesis.Tfh cell function is mostly regulated by T-follicular regulatory(Tfr)cells that are also located in the germinal center.This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis.New insights are provided into the potential for clinical application in GVHD prevention and treatment.

Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.

Function of Helper T Cells in the Memory CTL-mediated Anti-tumor Immunity

To investigate the role of CD4 + helper T (Th) cells in the memory CTL-mediated anti-tumor immunity, the RAG-1 gene knock out mice were adoptively transferred with OT-1 cells to generate the memory CTL, the C57BL/6 mice immunized with the epitope peptide of OVA specific Th cells and with different adjuvants were adoptively transferred with these memory-CTLs, and then the animals were challenged with tumor cells EG7. It was found that although the simple immunization of mice with the epitope peptide of the OVA specific Th cells could generate more effect CTL, but this effect was not so strong enough to resist completely the challenges with tumor cells. Nevertheless, the memory CTL-mediated anti-tumor immune effect required the helps of Th1 and Th2 cells. The cross-regulation between Th1 and Th2 cells seemed to be beneficial for the host to generate more effector CTL for mounting an efficient anti-tumor response. It concluded that the interaction between Th1 and Th2 cells might be more important than the single subset of Th cells in the memory CTL-mediated anti-tumor immune response. More attention should be paid in this regard for the future studies.

Analysis of the Peripheral Blood Helper T-Cell 17- Cell Level and Monocyte/Lymphocyte Ratio for Colorectal Cancer Prognosis Prediction

Objective: To investigate the value of peripheral blood helper T cell 17 cell level and monocyte/lymphocyte ratio to predict the prognosis of colorectal cancer patients. Methods: 74 colorectal cancer patients who attended Hospital 960 from January 2021 to January 2022 were retrospectively analyzed. Clinical data of the patients were collected, including gender, age, and histologic type. Immunohistochemical indexes such as Th17 cell level and monocyte/ lymphocyte ratio in the peripheral blood of patients were also collected. The prognosis of patients after treatment, as well as peripheral blood Th17 and MLR levels, were observed and analyzed. Results: After follow-up after treatment, in the final 74 patients, the prognosis was good in 32 patients, accounting for 43.24%, and the prognosis was bad in 42 patients, accounting for 56.76%. There were no significant differences between the average age and tumor diameters of the good prognosis and poor prognosis groups (P > 0.05). However, the TNM staging, intervention taken, differentiation degree, presence of distant metastasis, presence of lymph node metastasis, Th17 level, and MLR level are significantly different between the two groups (P < 0.05). Conclusion: Peripheral blood Th17 and MLR have predictive value for the prognosis of colorectal cancer patients, and high levels of peripheral blood Th17 and MLR imply poor prognosis. The detection of peripheral blood Th17 and MLR levels is simple and convenient and can be used as indicators to provide a reference for the prognostic assessment of colorectal cancer patients.

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients

Summary:The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease.Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic.In this study,we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia(FOP)patients who underwent lung surgery and served as controls.We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients.In contrast to the FOP patients,Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients.This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients.In summary,our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity.Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.

Matrine ameliorates experimental autoimmune encephalomyelitis by regulating the differentiation of encephalitogenic Th1/Th17 and Th2/regulatory T cells

OBJECTIVE Experimental autoimmune encephalomyelitis(EAE),the classical animal model for multiple sclerosis(MS)is triggered by an impaired balance of T helper(Th)cells and regulatory T(Tregs)cells.Matrine(MAT),a quinolizidine alkaloid derived from the herb Radix Sophorae Flave,has been shown to ameliorate the clinical signs,inflammatory infiltration,demyelination in acute EAE rats.However,whether MAT protect from EAE by adjusting Th and Treg cells response in specific-cellular and molecular level is unknown.METHODS Herein,MAT was tested for its effects on Th1,Th2,Th17 and Treg cells in the spinal cord of EAE mice and splenocyte-extracted from EAE mice with MOG35-55-restimulated,respectively.RESULTS Our findings revealed that MAT significantly inhibit the proliferation of splenocyte,and remarkably down-regulate the differentiation of Th1/Th17 cells with decreased expressions of CD4+IFN-γ+cells and CD4+IL-17+cells in vivo and IL-17,IFN-γ,ROR-γt,T-bet in vitro,meanwhile it dramatically up-regulate the Th2/Treg cells response associated with increased levels of CD4+TGF-β+1cells and CD4+IL-10+cells in vivo and IL-4,IL-10,TGF-β1,Foxp3 and GATA3in vitro.CONCLUSION Considering the effective therapeutic effects of MAT on EAE,it′s worth to find its new values on other autoimmune diseases.

Involvement of glycated albumin in adipose-derived-stem cellmediated interleukin 17 secreting T helper cell activation

BACKGROUND Advanced glycation end products(AGE)are a marker of various diseases including diabetes,in which they participate to vascular damages such as retinopathy,nephropathy and coronaropathy.Besides those vascular complications,AGE are involved in altered metabolism in many tissues,including adipose tissue(AT)where they contribute to reduced glucose uptake and attenuation of insulin sensitivity.AGE are known to contribute to type 1 diabetes(T1D)through promotion of interleukin(IL)-17 secreting T helper(Th17)cells.AIM To investigate whether lean adipose-derived stem cells(ASC)could be able to induce IL-17A secretion,with the help of AGE.METHODS As we have recently demonstrated that ASC are involved in Th17 cell promotion when they are harvested from obese AT,we used the same co-culture model to measure the impact of glycated human serum albumin(G-HSA)on human lean ASC interacting with blood mononuclear cells.IL-17A and pro-inflammatory cytokine secretion were measured by ELISA.Receptor of AGE(RAGE)together with intercellular adhesion molecule 1(ICAM-1),human leukocyte Antigen(HLA)-DR,cluster of differentiation(CD)41,and CD62P surface expressions were measured by cytofluorometry.Anti-RAGE specific monoclonal antibody was added to co-cultures in order to evaluate the role of RAGE in IL-17A production.RESULTS Results showed that whereas 1%G-HSA only weakly potentiated the production of IL-17A by T cells interacting with ASC harvested from obese subjects,it markedly increased IL-17A,but also interferon gamma and tumor necrosis factor alpha production in the presence of ASC harvested from lean individuals.This was associated with increased expression of RAGE and HLA-DR molecule by cocultured cells.Moreover,RAGE blockade experiments demonstrated RAGE specific involvement in lean ASC-mediated Th-17 cell activation.Finally,platelet aggregation and ICAM-1,which are known to be induced by AGE,were not involved in these processes.CONCLUSION Thus,our results demonstrated that G-HSA potentiated lean ASC-mediated IL-17A production in AT,suggesting a new mechanism by which AGE could contribute to T1D pathophysiology.

Dynamic interplay of T helpercell subsets in experimental autoimmune encephalomyelitis

AIM： To investigate the temporal onset and dynamic interplay of CD4^＋ T helper cell subsets in experimental autoimmune encephalomyelitis （EAE）.METHODS： EAE was induced in C57BL/6 mice by im-munization with myelin oligodendrocyte glycoprotein peptide p35-55. The clinical signs were scored and the tissue samples and immune cells isolated for analysis at different phases of EAE. The expression levels of inflammatory cytokines and related transcription fac-tors were detected by quantitative reverse transcription polymerase chain reaction （PCR） and enzyme linked immunosorbant assay （ELISA）. The percentages of Th1, Th17, Th2, Treg and memory T cell subsets in EAE were analyzed by immunostaining and fow cytometry. The data were analyzed by statistical techniques.RESULTS： Quantitative real-time PCR analysis showed that EAE mice express elevated levels of Th1 [interferon gamma （ IFNγ ）, interleukin （ IL ） -12p40 ], Th17 [ IL-17 , related orphan receptor gamma （RORγ ）, IL-12p40] and Treg [ Foxp3, Epstein-Barr virus induced gene 3 （EBI3）, IL-10] genes in the central nervous system at the peak of the disease. Whereas, the expression of Th1 （ IFNγ , T-bet, IL-12p35, IL-12p40 ）, Th17 （RORγ, IL-12p40 ）, Th2 （ IL-4） and Treg （ Foxp3, EBI3） response genes was reduced in the spleen during pre-disease but gradually recovered at the later phases of EAE. ELISA and fow cytometry analyses showed an increase in Th17 re-sponse in the periphery, while Th1 response remained unchanged at the peak of disease. The mRNA levels of IFNγ, IL-17 and IL-12p40 in the brain were increased by 23 （P 〈 0.001）, 9 （P 〈 0.05） and 14 （P 〈 0.01） fold, respectively, on day 21 of EAE. Conversely, the mRNA expression of IL-10 was increased by 2 fold （P 〈 0.05） in the spleen on day 21. CD4^＋CD25^＋Foxp3＋Treg response was reduced at pre-disease but recovered to na？ve levels by disease onset. The percentage of CD25 Foxp3 regulatory T cells decreased from 7.7% in the na？ve to 3.2% （P 〈 0.05） on day 7 of EAE, which then increased to 8.4% by day 28. Moreover, the CD4＋CD127＋CD44high memory T cell response was increased during the onset and recovery phases of EAE. The memory and effector cells showed an in-verse relationship in EAE, where the memory T cells increased from 12.3% in nave to 20% by day 21, and the effector cells decreased from 32% in na？ve to 21% （P 〈 0.01） by day 21. The wild type C57BL/6 mice with EAE showed elevated levels of effector-memory T cells （TEM） with concomitant reduction in central-memory T cells （TCM）, but the EAE-resistant IL-7R defcient mice showed elevated TCM with no effect on TEM cells in EAE.CONCLUSION： Our fndings highlight the temporal on-set and dynamic interplay of effector, memory and regu-latory CD4^＋ T cell subsets and its signifcance to clinical outcome in EAE and other autoimmune diseases.

Increased CD4^+CD45RA^-FoxP3^(low) cells alter the balance between Treg and Th17 cells in colitis mice

AIM To investigate the role of regulatory T cell(Treg) subsets in the balance between Treg and T helper 17(Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.METHODS T r e g c e l l s, T r e g c e l l s u b s e t s, T h 1 7 c e l l s, a n d CD4+CD25+FoxP 3+IL-17+ cells from the lamina propria of colon(LPC) and other ulcerative colitis(UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3(FoxP 3), interleukin 17A(IL-17A), and RORC m RNA levels were assessed by real-time PCR, while interleukin-10(IL-10) and IL-17 A levels were detected with a Cytometric Beads Array.RESULTS In peripheral blood monocytes(PBMC), mesenteric lymphnode(MLN), lamina propria of jejunum(LPJ) and LPC from UC mice, Treg cell numbers were increased(P < 0.05), and FoxP 3 and IL-10 mR NA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17 A levels in PBMC, LPJ, and serum. The number of FrI subset cells(CD4+CD45RA+FoxP 3low) was increased in the spleen, MLN, LPJ, and LPC. FrI I subset cells(CD4+CD45RA-Fox P3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of Fr III cells(CD4+CD45RA-FoxP 3low) and CD4+CD25+FoxP 3+IL-17A+ cells was increased. Fox P3 m RNA levels in CD4+CD45RA-Fox P3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17 A and RORC mR NA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP 3high, and CD4+CD45RA-FoxP 3low cells was higher in LPC relative to other tissues.CONCLUSION Increased numbers of CD4+CD45RA-FoxP 3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.

T helper cell dysregulation with hepatitis B and rebalance with glucocorticoids

AIM: To investigate T helper 17/regulatory T cell alterations in early severe hepatitis B and the effect of glucocorticoids.

Expression of Helper T Cell Type 17 and CD4^(+)CD25^(+)Tregs in AMA-M2 Positive PBC Patients

Objective:To investigate the expression and impact of helper T cell type 17 and CD4^(+)CD25^(+)regulatory T(Treg)cells in anti-mitochondrial M2 antibody(AMA-M2)positive primary biliary cholangitis(PBC)patients.Methods:Thirty PBC patients with positive AMA(M2 type)(antibody titer above 1:320)by indirect immunofluorescence assay under the Affiliated Hospital of Hebei University from November 2021 to August 2022 were selected as the experimental group,while 30 healthy individuals were selected as controls.The subjects were observed and analyzed for AFP-L3 and immunoglobulin expression.Results:The levels of Th17,Treg,Th17/Treg,interleukin(IL)-17A,IL-2,IL-10,and transforming growth factor(TGF)-β1 cytokines of the experimental group were 2.61±0.48,1.15±0.54,2.41±0.47,310.94±21.14,276.36±36.12,317.89±28.97,and 197.48±31.04,respectively,while those of the control group were 1.14±0.58,0.88±0.29,1.47±0.25,9.69±1.26,57.69±2.45,154.01±19.87,and 514.36±36.12,respectively,wherein P<0.05;the CD4^(+),CD8^(+),and CD4^(+)/CD8^(+)of the experimental group were 39.48±4.19,20.12±4.41,and 1.76±0.14,respectively,while those of the control group were 35.78±4.21,22.01±4.16,and 1.51±0.13,respectively,wherein P<0.05.Conclusion:In patients with PBC,there is a significant imbalance in Th17/Treg cells.Il-17A,IL-2,IL-10,and TGF-β1 cytokines play important roles in the differentiation and functional expression of both Th17 and Treg cells.