scholarly journals CD4 T Cells and Major Histocompatibility Complex Class II Expression Influence Worm Expulsion and Increased Intestinal Muscle Contraction during Trichinella spiralisInfection

1999 ◽  
Vol 67 (11) ◽  
pp. 6090-6097 ◽  
Author(s):  
Bruce A. Vallance ◽  
Francesca Galeazzi ◽  
Stephen M. Collins ◽  
Denis P. Snider
Keyword(s):  
T Cells ◽  
T Cell ◽  
Muscle Contraction ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Worm Expulsion ◽  
Deficient Mice

ABSTRACT Expulsion of intestinal nematode parasites and the associated increased contraction by intestinal muscle are T cell dependent, since both are attenuated in athymic rodents. The CD4 T-cell subset has been strongly associated with worm expulsion; however, the relationship between these cells, antigen presentation, and worm expulsion is not definitive and the role of these factors in intestinal muscle hypercontractility has not been defined. We infected C57BL/6, athymic, CD4-deficient, CD8α-deficient, and major histocompatibility complex class II (MHC II)-deficient (C2d) mice with Trichinella spiralis larvae. We examined intestinal worm numbers, longitudinal muscle contraction, and MHC II expression. Numerous MHC II-positive cells were identified within the muscularis externa of infected but not uninfected C57BL/6 mice. C57BL/6 and CD8α-deficient mice developed large increases in muscle contraction, expelling the parasite by day 21. Athymic and C2d mice exhibited much smaller increases in muscle contraction and delayed parasite expulsion. CD4-deficient mice exhibited intermediate levels of muscle contraction and delayed parasite expulsion. To further examine the role of MHC II and CD4 T cells, we irradiated C2d mice and reconstituted them with C57BL/6 bone marrow alone or with C57BL/6 CD4 T cells. C57BL/6 bone marrow alone did not affect muscle function or worm expulsion in recipient C2d mice. Partial CD4 T-cell reconstitution was sufficient to restore increased muscle contraction but not worm expulsion. Thus, hematopoietic MHC II expression alone is insufficient for the development of muscle hypercontractility and worm expulsion, but the addition of even small numbers of CD4 T cells was sufficient to induce intestinal muscle pathophysiology.

scholarly journals The critical role of CD4+ T cells in PD-1 blockade against MHC-II–expressing tumors such as classic Hodgkin lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4069-4082
Author(s):  
Joji Nagasaki ◽  
Yosuke Togashi ◽  
Takeaki Sugawara ◽  
Makiko Itami ◽  
Nobuhiko Yamauchi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Cd4 T Cell ◽  
Antitumor Effects ◽  
Cell Axis ◽  
Mhc I ◽  
Mhc Ii

Abstract Classic Hodgkin lymphoma (cHL) responds markedly to PD-1 blockade therapy, and the clinical responses are reportedly dependent on expression of major histocompatibility complex class II (MHC-II). This dependence is different from other solid tumors, in which the MHC class I (MHC-I)/CD8+ T-cell axis plays a critical role. In this study, we investigated the role of the MHC-II/CD4+ T-cell axis in the antitumor effect of PD-1 blockade on cHL. In cHL, MHC-I expression was frequently lost, but MHC-II expression was maintained. CD4+ T cells highly infiltrated the tumor microenvironment of MHC-II–expressing cHL, regardless of MHC-I expression status. Consequently, CD4+ T-cell, but not CD8+ T-cell, infiltration was a good prognostic factor in cHL, and PD-1 blockade showed antitumor efficacy against MHC-II–expressing cHL associated with CD4+ T-cell infiltration. Murine lymphoma and solid tumor models revealed the critical role of antitumor effects mediated by CD4+ T cells: an anti-PD-1 monoclonal antibody exerted antitumor effects on MHC-I−MHC-II+ tumors but not on MHC-I−MHC-II− tumors, in a cytotoxic CD4+ T-cell–dependent manner. Furthermore, LAG-3, which reportedly binds to MHC-II, was highly expressed by tumor-infiltrating CD4+ T cells in MHC-II–expressing tumors. Therefore, the combination of LAG-3 blockade with PD-1 blockade showed a far stronger antitumor immunity compared with either treatment alone. We propose that PD-1 blockade therapies have antitumor effects on MHC-II–expressing tumors such as cHL that are mediated by cytotoxic CD4+ T cells and that LAG-3 could be a candidate for combination therapy with PD-1 blockade.

scholarly journals Self major histocompatibility complex class I antigens expressed solely in lymphoid cells do not induce tolerance in the CD4+ T cell compartment.

1996 ◽  
Vol 184 (4) ◽  
pp. 1573-1578 ◽  
Author(s):  
R Schulz ◽  
A L Mellor
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Lymphoid Cells ◽  
Cd4 T Cell ◽  
Cell Compartment ◽  
Mhc I ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Self Peptides

Transgenic mice expressing self major histocompatibility complex (MHC) class I (H-2Kb) antigen solely in lymphoid cell lineages do not acquire tolerance to H-2Kb expressed on skin grafts. H-2Kb-specific cytotoxic T cell responses were completely abrogated in these mice, even after they had rejected skin grafts. Moreover, thymocytes expressing T cell receptors that confer H-2Kb reactivity on cytotoxic CD8+ T cells were eliminated. The ability to reject grafts correlated with the presence of a novel population of H-2Kb-reactive CD4+ T cells. At least some of these CD4+ T cells recognize peptides derived from H-2Kb by processing. We conclude that self MHC I antigens induce tolerance in the CD8 T cell compartment via negative selection when expressed exclusively by lymphoid cells. In contrast, tolerance to MHC class II-restricted self peptides derived by processing of such MHC I antigens is not induced in the CD4 T cell compartment. This suggests that effective transfer of self antigens from lymphoid cells to MHC II-positive cells that can process and present them as self peptides to thymocytes or CD4+ T cells does not take place in vivo. Thus, sequestration of self antigens and MHC II molecules in distinct cell types in the thymic microenvironment allows potentially autoreactive and functionally competent CD4+ T cells that recognize cryptic MHC II-restricted self peptides to mature into the peripheral T cell repertoire under normal physiological circumstances.

scholarly journals Cytomegalovirus-Specific CD4 T Cells Are Cytolytic and Mediate Vaccine Protection

2015 ◽  
Vol 90 (2) ◽  
pp. 650-658 ◽  
Author(s):  
Shilpi Verma ◽  
Daniela Weiskopf ◽  
Ankan Gupta ◽  
Bryan McDonald ◽  
Bjoern Peters ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Complex Class ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Class Ii Mhc

ABSTRACTCD4 T cells provide protection against cytomegalovirus (CMV) and other persistent viruses, and the ability to quantify and characterize epitope-specific responses is essential to gain a more precise understanding of their effector roles in this regard. Here, we report the first two I-Ad-restricted CD4 T cell responses specific for mouse CMV (MCMV) epitopes and use a major histocompatibility complex class II (MHC-II) tetramer to characterize their phenotypes and functions. We demonstrate that MCMV-specific CD4 T cells can express high levels of granzyme B and kill target cells in an epitope- and organ-specific manner. In addition, CD4 T cell epitope vaccination of immunocompetent mice reduced MCMV replication in the same organs where CD4 cytotoxic T lymphocyte (CTL) activity was observed. Together, our studies show that MCMV epitope-specific CD4 T cells have the potential to mediate antiviral defense by multiple effector mechanismsin vivo.IMPORTANCECD4 T cells mediate immune protection by using their T cell receptors to recognize specific portions of viral proteins, called epitopes, that are presented by major histocompatibility complex class II (MHC-II) molecules on the surfaces of professional antigen-presenting cells (APCs). In this study, we discovered the first two epitopes derived from mouse cytomegalovirus (MCMV) that are recognized by CD4 T cells in BALB/c mice, a mouse strain commonly used to study the pathogenesis of this virus infection. Here, we report the sequences of these epitopes, characterize the CD4 T cells that recognize them to fight off MCMV infection, and show that we can use the epitopes to vaccinate mice and protect against MCMV.

scholarly journals Isolevuglandin-Modified Cardiac Proteins Drive CD4+ T Cell Activation in the Heart and Promote Cardiac Dysfunction

Circulation ◽  
2021 ◽  
Author(s):  
Njabulo Ngwenyama ◽  
Annet Kirabo ◽  
Mark Aronovitz ◽  
Francisco Velázquez ◽  
Francisco Carrillo-Salinas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cardiac Dysfunction ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Myocardial Oxidative Stress

Background: Despite the well-established association between T cell-mediated inflammation and non-ischemic heart failure (HF), the specific mechanisms triggering T cell activation during the progression of HF and the antigens involved are poorly understood. We hypothesized that myocardial oxidative stress induces the formation of isolevuglandin (IsoLG)-modified proteins that function as cardiac neoantigens to elicit CD4+ T cell receptor (TCR) activation and promote HF. Methods: We used transverse aortic constriction (TAC) in mice to trigger myocardial oxidative stress and T cell infiltration. We profiled the TCR repertoire by mRNA sequencing of intramyocardial activated CD4+ T cells in Nur77 GFP reporter mice, which transiently express GFP upon TCR engagement. We assessed the role of antigen presentation and TCR specificity in the development of cardiac dysfunction using antigen presentation-deficient MhcII -/- mice, and TCR transgenic OTII mice that lack specificity for endogenous antigens. We detected IsoLG-protein adducts in failing human hearts. We also evaluated the role of reactive oxygen species (ROS) and IsoLGs in eliciting T cell immune responses in vivo by treating mice with the antioxidant TEMPOL, and the IsoLG scavenger 2-hydroxybenzylamine (2-HOBA) during TAC, and ex-vivo in mechanistic studies of CD4+ T cell proliferation in response to IsoLG-modified cardiac proteins. Results: We discovered that TCR antigen recognition increases in the left ventricle (LV) as cardiac dysfunction progresses, and identified a limited repertoire of activated CD4+ T cell clonotypes in the LV. Antigen presentation of endogenous antigens was required to develop cardiac dysfunction since MhcII -/- mice reconstituted with CD4+ T cells, and OTII mice immunized with their cognate antigen were protected from TAC-induced cardiac dysfunction despite the presence of LV-infiltrated CD4+ T cells. Scavenging IsoLGs with 2-HOBA reduced TCR activation and prevented cardiac dysfunction. Mechanistically, cardiac pressure overload resulted in ROS dependent dendritic cell accumulation of IsoLG-protein adducts which induced robust CD4+ T cell proliferation. Conclusions: Collectively, our study demonstrates an important role of ROS-induced formation of IsoLG-modified cardiac neoantigens that lead to TCR-dependent CD4+ T cell activation within the heart.

scholarly journals Telomerase and CD4 T Cell Immunity in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1687
Author(s):  
Magalie Dosset ◽  
Andrea Castro ◽  
Hannah Carter ◽  
Maurizio Zanetti
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Tumor Formation ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
Current Status ◽  
Mhc Ii ◽  
Cell Immunity

Telomerase reverse transcriptase (TERT) is a conserved self-tumor antigen which is overexpressed in most tumors and plays a critical role in tumor formation and progression. As such, TERT is an antigen of great relevance to develop widely applicable immunotherapies. CD4 T cells play a major role in the anti-cancer response alone or with other effector cells such as CD8 T cells and NK cells. To date, efforts have been made to identify TERT peptides capable of stimulating CD4 T cells that are also able to bind diverse MHC-II alleles to ease immune status monitoring and immunotherapies. Here, we review the current status of TERT biology, TERT/MHC-II immunobiology, and past and current vaccine clinical trials. We propose that monitoring CD4 T cell immunity against TERT is a simple and direct way to assess immune surveillance in cancer patients and a new way to predict the response to immune checkpoint inhibitors (ICPi). Finally, we present the initial results of a systematic discovery of TERT peptides able to bind the most common HLA Class II alleles worldwide and show that the repertoire of MHC-II TERT peptides is wider than currently appreciated.

scholarly journals Second Class Minors

2003 ◽  
Vol 197 (3) ◽  
pp. 375-385 ◽  
Author(s):  
Hiroeki Sahara ◽  
Nilabh Shastri
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Interleukin 4 ◽  
General Strategy ◽  
Mhc Ii ◽  
Cell Responses ◽  
Antigen Presenting

CD4 T cells regulate immune responses that cause chronic graft rejection and graft versus host disease but their target antigens remain virtually unknown. We developed a new method to identify CD4 T cell–stimulating antigens. LacZ-inducible CD4 T cells were used as a probe to detect their cognate peptide/MHC II ligand generated in dendritic cells fed with Escherichia coli expressing a library of target cell genes. The murine H46 locus on chromosome 7 was thus found to encode the interleukin 4–induced IL4i1 gene. The IL4i1 precursor contains the HAFVEAIPELQGHV peptide which is presented by Ab major histocompatibility complex class II molecule via an endogenous pathway in professional antigen presenting cells. Both allelic peptides bind Ab and a single alanine to methionine substitution at p2 defines nonself. These results reveal novel features of H loci that regulate CD4 T cell responses as well as provide a general strategy for identifying elusive antigens that elicit CD4 T cell responses to tumors or self-tissues in autoimmunity.

Promoting Regulation Via the Inhibition of DNAM-1 After Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 338-338
Author(s):  
Motoko Koyama ◽  
Rachel D Kuns ◽  
Stuart D Olver ◽  
Katie E Lineburg ◽  
Mary Lor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Steady State ◽  
T Cell ◽  
Median Survival ◽  
Cd4 T Cells ◽  
Cell Expansion ◽  
Acute Gvhd ◽  
Cd4 T Cell

Abstract Abstract 338 Graft-versus-host disease (GVHD) is the major limitation of allogeneic hematopoietic bone marrow transplantation (BMT). Donor T cells play pivotal roles in GVHD and graft-versus-leukemia (GVL) effects and following BMT all T cell fractions, including regulatory T cells (Treg) express the DNAX accessory molecule-1 (DNAM-1, CD226) and T cell Immunoglobulin and ITIM domain (TIGIT) molecule. DNAM-1 is a co-stimulatory and adhesion molecule, expressed mainly by NK cells and CD8+ T cells at steady state to promote adhesion to ligand (CD155, CD112)–expressing targets and enhance cytolysis. TIGIT is a regulatory ligand expressed predominantly by Treg as steady state which competes for CD155 binding, We have analyzed the role of this pathway in GVHD and GVL. Lethally irradiated C3H/Hej (H-2k) mice were injected with bone marrow cells and T cells from MHC disparate wild-type (wt) or DNAM-1–/– C57Bl6 (H-2b) mice. Recipients of DNAM-1–/– grafts were protected from GVHD (survival 67% vs. 7%, P < .0001). We also confirmed the role of DNAM-1 in GVHD in a MHC-matched BMT model (B6 → BALB/B (H-2b)) where GVHD is directed to multiple minor histocompatibility antigens. Next we examined the donor populations expressing DNAM-1 which mediate this effect. DNAM-1 had little impact on acute GVHD severity in the B6 → bm1 BMT model where GVHD is directed against an isolated MHC class I mismatch and is CD8-dependent. In contrast, recipients of wt bone marrow and DNAM-1–/– CD4 T cells survived long-term (compared to recipients of wt CD4 T cells, survival 81% vs. 25%, P = .003) in the B6 → B6C3F1 BMT model, confirming the protection from GVHD is CD4-dependent. Donor CD4 T cell expansion and effector function (Th1 and Th17), and CD8 T cell expansion and cytotoxic function were equivalent in recipients of wt and DNAM-1–/– grafts. However the percentage and number of Treg were significantly increased in recipients of DNAM-1–/– grafts compared to those of wt grafts. The depletion of Treg from donor grafts eliminated the protection from GVHD seen in the absence of DNAM-1 signalling (median survival 16 days vs. 15.5 days, P = 0.53). Adoptive transfer experiments using FACS-sorted Treg were undertaken to compare the relative ability of B6.WT and B6.DNAM-1–/– Treg to suppress GVHD. The majority of recipients of DNAM-1–/– Treg survived beyond day 50 (median survival; day 56), demonstrating a superior ability to suppress acute GVHD relative to wt Treg where the median survival was day 36 (survival 47% vs. 0%, P = .001). These data demonstrate that donor DNAM-1 expression promotes GVHD in a CD4+ T cell-dependent manner via the inhibition of donor Foxp3+ Treg. Finally, the absence of donor DNAM-1 did not influence leukemia-specific mortality in multiple GVL models, regardless of whether the tumor expressed CD155 or not. Thus we demonstrate that the DNAM-1 pathway promotes GVHD, putatively due to competition with TIGIT on Treg, thereby inhibiting regulatory function. This provides support for therapeutic DNAM-1 inhibition to promote tolerance not only after transplant but also in relevant inflammatory based diseases characterized by T cell activation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Organ- and Disease-Stage-Specific Regulation of Toxoplasma gondii-Specific CD8-T-Cell Responses by CD4 T Cells

2006 ◽  
Vol 74 (10) ◽  
pp. 5790-5801 ◽  
Author(s):  
Sonja Lütjen ◽  
Sabine Soltek ◽  
Simona Virna ◽  
Martina Deckert ◽  
Dirk Schlüter
Keyword(s):  
T Cells ◽  
T Cell ◽  
Toxoplasma Gondii ◽  
Cd8 T Cells ◽  
Functional Activity ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Ifn Γ

ABSTRACT Toxoplasma gondii induces a persistent central nervous system infection, which may be lethally reactivated in AIDS patients with low CD4 T-cell numbers. To analyze the role of CD4 T cells for the regulation of parasite-specific CD8 T cells, mice were infected with transgenic T. gondii expressing the CD8 T-cell antigen β-galactosidase (β-Gal). Depletion of CD4 T cells prior to infection did not affect frequencies of β-Gal876-884-specific (consisting of residues 876 to 884 of β-Gal) CD8 T cells but resulted in a pronounced reduction of intracerebral β-Gal-specific gamma interferon (IFN-γ)-producing and cytolytic CD8 T cells. After cessation of anti-CD4 treatment a normal T. gondii-specific CD4 T-cell response developed, but IFN-γ production of intracerebral β-Gal-specific CD8 T cells remained impaired. The important supportive role of CD4 T cells for the optimal functional activity of intracerebral CD8 T cells was also observed in mice that had been depleted of CD4 T cells during chronic toxoplasmosis. Reinfection of chronically infected mice that had been depleted of CD4 T cells during either the acute or chronic stage of infection resulted in an enhanced proliferation of β-Gal-specific IFN-γ-producing splenic CD8 T cells. However, reinfection of chronically infected mice that had been depleted of CD4 T cells in the acute stage of infection did not reverse the impaired IFN-γ production of intracerebral CD8 T cells. Collectively, these findings illustrate that CD4 T cells are not required for the induction and maintenance of parasite-specific CD8 T cells but, depending on the stage of infection, the infected organ and parasite challenge infection regulate the functional activity of intracerebral CD8 T cells.

scholarly journals The E3 Ubiquitin Ligase Cbl-b Limits Nascent Th9 Differentiation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2222-2222
Author(s):  
Isabelle Cornez ◽  
Sowmya Parampalli Yajnanarayana ◽  
Natascha Hermann-Kleiter ◽  
Stefan Ulrich Schmidt ◽  
Peter Brossart ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ubiquitin Ligase ◽  
Cd4 T Cells ◽  
Lung Inflammation ◽  
E3 Ubiquitin Ligase ◽  
Th9 Cells ◽  
Deficient Mice ◽  
Th9 Cell

Abstract Introduction: Th9 cells are critical mediators of allergy and anti-cancer immunity. The E3 ubiquitin ligase Cbl-b modulates T cell activation via regulation of the T cell receptor (TCR) activation threshold as well as by inducing TGF-β sensitivity, which is a critical differentiation factor for Th9 differentiation. Even though some evidence shows that Cbl-b impairs Th9 differentiation by targeting IL-4 dependent STAT6 activation, a complete suppression of Th9 differentiation in the absence of both STAT6 and Cbl-b is not achieved, implying the involvement of additional mechanisms. In this study, we evaluate the role of Cbl-b in early stages of TGF-β dependent Th9 differentiation. Methods: Th9 cells were generated from WT and cblb-deficient naïve CD4+ T cells. After maximum 3 days in presence of IL-4, TGF-β and anti-IFN-γ antibodies, differentiation was determined by the quantification of cytokines, mainly IL-9, and that of the two required transcription factors for Th9 differentiation, namely IRF4 and PU.1. Microarray assay revealed gene candidates that were further validated by mRNA and protein expression analysis. The functional role of Cbl-b was tested in a Th9-mediated murine lung allergy model, in which mice were challenged by intratracheal injections of house dust mite (HDM) extracts. Results: cblb-deficient naïve T cells more efficiently differentiate into Th9 cells after 3 days in culture, express in parallel PU.1 more intensively compared to WT Th9 cells, while retaining similar expression levels of IRF4, another important Th9 differentiation factor. Increased IL-9 level is not based on cblb -deficient T cell hyperproliferation, as we show an increased IL-9 production per cell by using combination of CFSE with intracellular IL-9 staining. Microarray analysis revealed that RUNX1, a known transcriptional modulator of PU.1, is more rapidly down-regulated in cblb-deficient Th9 cells compared to WT Th9 cells. Accordingly, knocking down RUNX1 by siRNA in naïve CD4+ T cells and subsequently differentiating them into Th9 cells, also induces higher IL-9 expression at the mRNA and protein levels in RUNX1-depleted Th9 cells compared to control scrambled siRNA-nucleofected Th9 cells. In the HDM murine allergy model, cblb-deficient mice have a higher lung inflammation as mirrored by increased eosinophils in the BAL and in the lungs, as well as by increased IgE production in the blood. These are also paralleled by an increased IL-9 expression level in the lungs of the allergic cblb -deficient mice. Conclusions: Cbl-b critically limits Th9 differentiation and may thus be a potential target to modify Th9 cell generation in allergy or cancer. Future studies will validate the molecular link that exists between Cbl-b and the RUNX1-dependent IL-9 expression as well as the in vivo significance of increased Th9 cell differentiation in cblb-deficient animal models of lung inflammation and cancer. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Role of β-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Kunlong Xiong ◽  
Jinxia Niu ◽  
Ruijuan Zheng ◽  
Zhonghua Liu ◽  
Yanzheng Song ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cd4 T Cell ◽  
Cell Frequency ◽  
Tnf Α ◽  
Ifn Γ

β-Catenin is a key molecule of canonical Wnt/β-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of β-catenin in CD4+ T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4+ T cell-specific β-catenin conditional knockout mice (β-CAT-cKO mice) were aerosol infected with Mycobacteria tuberculosis (Mtb) H37RV with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-γ, TNF-α, and TCF-7 in the lungs of mice was measured. CD4, CD8, β-catenin, IFN-γ, and TNF-α in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of β-catenin, IFN-γ, TNF-α, and PD-1 in CD4+ and CD8+ T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-γ/TNF-α mRNA expression and secretion by CD4+ T cells in the lungs of infected β-CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. β-catenin expressions in CD4+ and CD8+ T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of β-catenin, resulted in the increase in CD4+ T cell frequency, as well as their secretion of IFN-γ and TNF-α. β-Catenin demonstrated a moderately positive correlation with PD-1 in CD4+ T cells. β-Catenin along with PD-1 and IFN-γ in CD4+ T cells had a high correlation with those in CD8+ T cells. In conclusion, β-catenin may be involved in the regulation of Th1 response and CD4+ T cell frequency in TB.

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