scholarly journals Chemokine receptor expression on peripheral blood T-helper cells in Helicobacter pylori-associated diseases: chronic gastroduodenitis and peptic ulcer disease

2019 ◽  
Vol 9 (2) ◽  
pp. 295-303
Author(s):  
V. Yu. Talayev ◽  
M. V. Talaeyva ◽  
E. V. Voronina ◽  
I. Ye. Zaichenko ◽  
N. V. Neumoina ◽  
...  
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
T Cell ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Chemokine Receptors ◽  
T Helper ◽  
Helper Cells ◽  
H Pylori

Helicobacter pylorirepresents a pathogen causing chronic infection in around a half of the global human population, which manifestations vary from asymptomatic infection to developing gastritis and peptic ulcer. The data accumulated suggest that overt clinical types of this infection are associated with lost immunoregulation and increased pro-inflammatory cell-mediated immune response triggered byH. pylori-specific T helper cells. Here, we examined the degree of peripheral blood CD4+T cell maturity and related expression of chemokine receptors involved in migration to gastrointestinal tract (CCR9 and CCR6), as well as Тand B-cell zones of lymphoid organs (CCR7 and CXCR5). It was shown that overtH. pylori-infection was coupled to changes in expression pattern of chemokine receptors on T helper cells. In particular, percentage of mature CD4+CD45RO+T cells bearing CCR9 and immature CD4+CD45RO–Т cells expressing CXCR5 was increased in peripheral blood of patients with chronic gastroduodenitis. However, increased amount of activated mature CD4+CD45RO+ICOS+T cells was observed in patients with chronic gastroduodenitis comorbid with peptic ulcer that was also associated with elevated amount of mature CCR6+T helpers (mainly CD4+CD45RO+CCR7–CCR6+cells) and follicular T helper cells as well as emerging minor CD4+CD45RO+CXCR5+CCR6+.T cell subset, not affecting CD4+CCR9+Т cells. Thus, the data obtained evidence that tissue-specific T-helper cell migration is controlled separately in ofH. pylori-associated diseases. 

scholarly journals Neonatal lymphocyte subpopulations analysis and maternal preterm premature rupture of membranes: a pilot study

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Margherita Amadi ◽  
Silvia Visentin ◽  
Francesca Tosato ◽  
Paola Fogar ◽  
Giulia Giacomini ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Helper Cells ◽  
Lymphocyte Subpopulations ◽  
T Helper ◽  
Premature Rupture Of Membranes ◽  
Premature Rupture ◽  
Preterm Premature Rupture ◽  
Helper Cells

Abstract Objectives Preterm premature rupture of membranes (pPROM) causes preterm delivery, and increases maternal T-cell response against the fetus. Fetal inflammatory response prompts maturation of the newborn’s immunocompetent cells, and could be associated with unfavorable neonatal outcome. The aims were to examine the effects of pPROM (Mercer BM. Preterm premature rupture of the membranes: current approaches to evaluation and management. Obstet Gynecol Clin N Am 2005;32:411) on the newborn’s and mother’s immune system and (Test G, Levy A, Wiznitzer A, Mazor M, Holcberg G, Zlotnik A, et al. Factors affecting the latency period in patients with preterm premature rupture of membranes (pPROM). Arch Gynecol Obstet 2011;283:707–10) to assess the predictive value of immune system changes in neonatal morbidity. Methods Mother-newborn pairs (18 mothers and 23 newborns) who experienced pPROM and controls (11 mothers and 14 newborns), were enrolled. Maternal and neonatal whole blood samples underwent flow cytometry to measure lymphocyte subpopulations. Results pPROM-newborns had fewer naïve CD4 T-cells, and more memory CD4 T-cells than control newborns. The effect was the same for increasing pPROM latency times before delivery. Gestational age and birth weight influenced maturation of the newborns’ lymphocyte subpopulations and white blood cells, notably cytotoxic T-cells, regulatory T-cells, T-helper cells (absolute count), and CD4/CD8 ratio. Among morbidities, fewer naïve CD8 T-cells were found in bronchopulmonary dysplasia (BPD) (p=0.0009), and more T-helper cells in early onset sepsis (p=0.04). Conclusions pPROM prompts maturation of the newborn’s T-cell immune system secondary to antigenic stimulation, which correlates with pPROM latency. Maternal immunity to inflammatory conditions is associated with a decrease in non-major histocompatibility complex (MHC)-restricted cytotoxic cells.

scholarly journals Tissue-resident CD4+ T helper cells assist the development of protective respiratory B and CD8+ T cell memory responses

2021 ◽  
Vol 6 (55) ◽  
pp. eabb6852
Author(s):  
Young Min Son ◽  
In Su Cheon ◽  
Yue Wu ◽  
Chaofan Li ◽  
Zheng Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Helper Cells ◽  
Critical Role ◽  
Cell Formation ◽  
Influenza Virus Infection ◽  
T Helper ◽  
Helper Cells ◽  
Cell Immunity

Much remains unknown about the roles of CD4+ T helper cells in shaping localized memory B cell and CD8+ T cell immunity in the mucosal tissues. Here, we report that lung T helper cells provide local assistance for the optimal development of tissue-resident memory B and CD8+ T cells after the resolution of primary influenza virus infection. We have identified a population of T cells in the lung that exhibit characteristics of both follicular T helper and TRM cells, and we have termed these cells as resident helper T (TRH) cells. Optimal TRH cell formation was dependent on transcription factors involved in T follicular helper and resident memory T cell development including BCL6 and Bhlhe40. We show that TRH cells deliver local help to CD8+ T cells through IL-21–dependent mechanisms. Our data have uncovered the presence of a tissue-resident helper T cell population in the lung that plays a critical role in promoting the development of protective B cell and CD8+ T cell responses.

scholarly journals Tissue-resident CD4+ T helper cells assist protective respiratory mucosal B and CD8+ T cell memory responses

2020 ◽  
Author(s):  
Young Min Son ◽  
In Su Cheon ◽  
Yue Wu ◽  
Chaofan Li ◽  
Zheng Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Helper Cells ◽  
Cell Formation ◽  
Influenza Virus Infection ◽  
T Helper ◽  
Helper Cells ◽  
Mucosal Tissues ◽  
Cell Immunity ◽  
Cd8 T Cell Memory

AbstractThe roles of CD4+ T helper cells (TH) in shaping localized memory B and CD8+ T cell immunity in the mucosal tissues are largely unexplored. Here, we report that lung TH cells provide local assistance for the optimal development of tissue-resident memory B (BRM) and CD8+ T (TRM) cells following the resolution of primary influenza virus infection. We identify a population of tissue-resident CD4+ TH (aka TRH) cells that co-exhibit follicular T helper (TFH) and TRM cell features and mediate local help of CD4+ T cells to B and CD8+ T cells. Optimal TRH cell formation requires lung B cells and transcription factors involved in TFH or TRM development. Further, we show that TRH cells deliver local help to B and CD8 T cells through CD40L and IL-21-dependent mechanisms. Our data have uncovered a new tissue-resident TH cell population that is specialized in assisting the development of mucosal protective B and CD8+ T cell responses in situ.

scholarly journals Ripk3 Signaling Restricts the Development of Peripheral T Cell Lymphoma in Tet2 Deficient Mice

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3318-3318
Author(s):  
Kanak Joshi ◽  
Ryan Mack ◽  
Lei Zhang ◽  
Shanhui Liu ◽  
Mark Sellin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
T Helper Cells ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Wild Type ◽  
T Helper ◽  
Peripheral T Cell Lymphoma ◽  
Helper Cells

Abstract Inactive mutations of the Ten-eleven translocation (TET2) gene are commonly found in humans with multiple hematological malignancies including myeloproliferative neoplasm (MPN), acute myeloid leukemia, diffuse large B cell lymphoma, and peripheral T cell lymphomas (PTCL), and are frequently associated with poor prognosis and worse overall survival. TET2 mutations often occur in hematopoietic stem and progenitor cells (HSPCs) and are known to collaborate with additional mutations for full-blown malignant transformation. However, the molecular mechanism by which the disease identity is determined remains to be elucidated. Increased inflammatory cytokines are commonly detected in patients with TET2 mutations, which is associated with an increased risk of atherosclerotic cardiovascular diseases. Most Tet2 knockout (Tet2 -/-) mice develop MPN-like disease within 18 months, with only a few cases developing chronic lymphocyte leukemia-like disease at two years of age. The intestinal bacteria-induced inflammatory signaling plays a critical role in the pathogenesis of MPN-like disease in Tet2 -/- mice. Receptor-interacting protein kinase 3 (Ripk3) is a key mediator of inflammation cytokine-induced necroptosis and metabolic signaling. Compared to bone marrow (BM) cells isolated from wild-type mice, higher levels of Ripk3 activity can be detected in Tet2 -/- BM cells. To study the role of Ripk3 in Tet2 mutations associated with hematopoietic diseases, we crossed Tet2 conditional knockout (Tet2fx/fx Mx1-Cre +) mice with Ripk3 -/- mice to generate Tet2 and Ripk3 compound knockout (Tet2 -/-Ripk3 -/-) mice. Tet2 -/-Ripk3 -/- mice developed aggressive tumors by 12-15 months of age as characterized by profound hepatosplenomegaly and lymphadenopathy, with substantial lymphocytosis, neutrophilia, anemia, and thrombocytopenia. Histopathological analysis revealed an aggressive infiltration of tumor cells in the liver and spleen, and effacement of splenic follicular structures in diseased Tet2 -/-Ripk3 -/- mice. To characterize the type of malignancies, single-cell suspensions of the BM, peripheral blood (PB), and spleen from Tet2 -/-Ripk3 -/- were analyzed by flow cytometry and compared with wild-type and Tet2 -/- mice. As expected Tet2 -/- mice exhibited increased frequencies of myeloid cells in the PB, BM, and spleen. However, there was a marked expansion of CD4 + T cells in the PB, BM, and spleen of Tet2 -/-Ripk3 -/- mice. Detailed analyses of the T subsets demonstrated a marked expansion of both CD4 +PD1 +CXCR5 + follicular T helper cells (T fh) and CD4 +PD1 + peripheral T helper cells (T ph), indicating the development of a peripheral T cell lymphoma (PTCL) in the Tet2 -/-Ripk3 -/- mice. Additionally, disease characteristics including the reduced surface expression of CD3 in the tumor cells, increased levels of classical T h cytokines in the serum, as well as the presence of heterogeneous populations of cells within the tumor tissues recapitulate the pathological features of angioimmunoblastic T cell lymphoma (AITL), a subtype of PTCL. Elevated frequencies of splenic T fh and T ph cells were detected as early as 7 months of age in Tet2 -/-Ripk3 -/- mice. Such cells expressed inducible T cell costimulatory receptor (ICOS), an essential signaling mediator of the T fh development and proliferation. However, all other hematopoietic parameters including BM HSPCs and mature CD4 + T cells were comparable to wild type and single-gene Tet2 -/- mice. These results indicate that Ripk3 signaling inhibits PTCL development in Tet2 -/- mice by limiting the expansion of T fh and T ph cells. We are currently determining whether Ripk3 plays such a role by inducing necroptosis and/or restricting the differentiation of CD4 + naive T cells into peripheral T fh and T ph populations. We are also investigating whether Ripk3 signaling is inactivated in the tumor cells of human PTCL patients and whether we can treat such aggressive fatal diseases by reactivating Ripk3 signaling. Disclosures No relevant conflicts of interest to declare.

scholarly journals Authentic T helper CD4 (W3/25) antigen on rat peritoneal macrophages.

1985 ◽  
Vol 162 (1) ◽  
pp. 117-127 ◽  
Author(s):  
W A Jefferies ◽  
J R Green ◽  
A F Williams
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibody ◽  
T Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cells ◽  
T Helper Cells ◽  
Peritoneal Macrophages ◽  
T Helper ◽  
Helper Cells

The rat W3/25 antigen that appears to be equivalent to human CD4 (T4) antigen is expressed on thymocytes and T helper cells and plays a role in the response of T helper cells to antigen. The W3/25 and anti-T4 antibodies also label macrophages. In this paper we examine whether the macrophage antigen is the same as that on T cells. New monoclonal antibodies against the rat CD4 antigen, MRC OX-35 through OX-38, are described, all of which label peritoneal macrophages from normal and athymic rats. The molecular weight of W3/25 antigen on macrophages is indistinguishable from that on T cells. We conclude that macrophages express authentic CD4 (W3/25) antigen. Another new monoclonal antibody, MRC OX-34, labels an antigen of 50-54,000 mol wt that is expressed on rat T but not B cells or peritoneal macrophages. It was used to control for the presence of any T cell products in immunoprecipitation from rat macrophage extracts.

Patologic IL 17 Producing Helper T Cells In Acute Myeloid Leukemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2289-2289
Author(s):  
Gerardo Musuraca ◽  
Serena De Matteis ◽  
Roberta Napolitano ◽  
Francesco Fabbri ◽  
Delia Cangini ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Th17 Cells ◽  
Myeloid Leukemia ◽  
Helper T Cells ◽  
T Helper ◽  
Helper Cells ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) remains the most common form of acute leukemia in adults but the treatments, in the past several decades, have not led to satisfactory results. Serious infections and therapy resistance or relapsed are the main causes of mortality among these patients. IL-17 producing helper T cells (Th17) play in humans, pleiotropic roles in protection against a range of predominantly extracellular bacterial and fungal pathogens, in the pathogenesis of many inflammatory and autoimmune diseases and a controversial role in protection or progression of tumors. In particular, recently has been demonstrated a remarkable plasticity of these cells to transdifferentiate, depending of the stimuli, in a Th1-like Th17 cells (secreting IFNg with tumor suppressor activity) or in a Treg-like Th17 cells (secreting IL-10 with tumor promoter activity). Moreover, few reports indicate that the number of Th17 in patients with hematological malignancies was increased in peripheral blood, however their role and their relationship with respect to other T helper cells, particularly in AML, have not yet been clarified. Our study aims to investigate the role of T helper cells in AML, with particular focus to Th17 cells, hypothesizing their contribution in severe infections developed by these patients and in the high rate of recurrence of the disease. Samples of peripheral blood were collected from 20 newly diagnosed AML patients of any FAB (except promyelocitic) before any treatment and 20 sex and age-matched healthy volunteers. Mononuclear cells (PBMCs) were separated by density gradient centrifugation. Intracellular IFN-γ, IL-17A and IL-4 expression was performed using the human Th1/Th2/Th17 phenotyping kit after stimulation of CD4+ cells with IL-6 (25 μg/ml), phorbol 12-myristate-13-acetate (50 ng/ml) and ionomycin (1 μg/ml). For Tregs analysis, PBMCs were stained with anti-human FITC CD4, APC-Cy7 CD25 and APC Foxp3 and analyzed using a FACSCanto flow cytometer. For the analysis of cytokine secretion, human IL-17 and IL-10 secretion - detection kits were used. Th1 and Th2 percentages were lower in untreated patients (3.4 ± 1.9% and 0.8 ± 0.6% respectively) than in controls (11.6 ± 4.0% and 2.5 ± 1.9% respectively) whereas the Th17 cells were increased in AML patients (1.9 ± 1.2%) in comparison to healthy donors (1.0 ± 0.6) (Fig. 1). All the observed differences were statistically significant. The frequency of CD4+ CD25+ FoxP3+ cells was statistically significant higher in AML samples (5.6 ± 3.0%) than in controls (2.7 ± 0.9%) (Fig 2). Moreover we observed in AML patients, no differences in the frequency of IFN-g/IL-17A double-producing T cells (0.7 ± 0.7%) compared to controls (0.54 ± 0.37%) whereas interestingly we observed an increase in the frequency of IL-10/IL-17A secreting T cells (0.18 ± 0.14% for patients vs. 0.02 ± 0.04% for donors) (Fig. 3). These results strongly suggest the hypothesis that in AML patients, probably through particular stimuli, cancer cells are able to transform the immunological environment (in particular the Th17 activity), towards a state of immunosuppression that promotes the development of infection and reduces the immunological control of the disease and relapses. This finding, if confirmed, could suggest new therapeutic strategies more oriented towards immunomodulation rather than cytoreduction. Disclosures: Martinelli: NOVARTIS, BMS(Consultancy and speaker bureau), PFIZER, ARIAD (Consultancy): Consultancy, Speakers Bureau.

Vaccine-Induced, Pseudorabies Virus-Specific, Extrathymic CD4+CD8+ Memory T-Helper Cells in Swine

1998 ◽  
Vol 72 (6) ◽  
pp. 4866-4873 ◽  
Author(s):  
Bertram T. Ober ◽  
Artur Summerfield ◽  
Christina Mattlinger ◽  
Karl-Heinz Wiesmüller ◽  
Günther Jung ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
T Helper Cells ◽  
Pseudorabies Virus ◽  
Class Ii ◽  
T Cell Epitopes ◽  
T Helper ◽  
Helper Cells

ABSTRACT Pseudorabies virus (PRV; suid herpesvirus 1) infection causes heavy economic losses in the pig industry. Therefore, vaccination with live attenuated viruses is practiced in many countries. This vaccination was demonstrated to induce extrathymic virus-specific memory CD4+CD8+ T lymphocytes. Due to their major histocompatibility complex (MHC) class II-restricted proliferation, it is generally believed that these T lymphocytes function as memory T-helper cells. To directly prove this hypothesis, 15-amino-acid, overlapping peptides of the viral glycoprotein gC were used for screening in proliferation assays with peripheral blood mononuclear cells of vaccinated d/d haplotype inbred pigs. In these experiments, two naturally processed T-cell epitopes (T1 and T2) which are MHC class II restricted were identified. It was shown that extrathymic CD4+CD8+ T cells are the T-lymphocyte subpopulation that responds to epitope T2. In addition, we were able to show that cytokine secretion can be induced in these T cells through recall with inactivated PRV and demonstrated that activated PRV-primed CD4+CD8+ T cells are able to induce PRV-specific immunoglobulin synthesis by PRV-primed, resting B cells. Taken together, these results demonstrate that the glycoprotein gC takes part in the priming of humoral anti-PRV memory responses. The experiments identified the first T-cell epitopes so far known to induce the generation of virus-specific CD4+CD8+ memory T lymphocytes and showed that CD4+CD8+ T cells are memory T-helper cells. Therefore, this study describes the generation of virus-specific CD4+CD8+ T cells, which is observed during vaccination, as a part of the potent humoral anti-PRV memory response induced by the vaccine.

Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate

2009 ◽  
Vol 16 (2) ◽  
pp. 218-227 ◽  
Author(s):  
M. Chiarini ◽  
A. Sottini ◽  
C. Ghidini ◽  
C. Zanotti ◽  
F. Serana ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Glatiramer Acetate ◽  
T Helper Cells ◽  
T Cell Repertoire ◽  
T Helper ◽  
Cell Repertoire ◽  
Helper Cells ◽  
Cell Diversity ◽  
Multiple Sclerosis Patients

The immunomodulating activity of glatiramer acetate on T-cells of multiple sclerosis patients has only been partially clarified. The objective of this work was to investigate whether glatiramer acetate modifies thymic release of newly produced T-cells and the peripheral composition of the T-cell repertoire. T-cell receptor excision circles, thymic naive (CD4+CD45RA+CCR7 +CD31+) T helper cells, and central (CD4+CD45RA -CCR7+) and effector (CD4+CD45RA-CCR7 -) memory T-cells were evaluated in 89 untreated patients, 84 patients treated for at least 1 year, and 31 patients beginning treatment at the time of inclusion in the study and then followed-up for 12 months; controls were 81 healthy donors. The T-cell repertoire was analysed in selected samples. The percentage of thymicnaive T helper cells was diminished in untreated patients, but rose to control values in treated subjects; a decrease in central memory T-cells was also observed in treated patients. Follow-up patients could be divided into two subgroups, one showing unmodified thymicnaive T helper cells and T-cell diversity, the other in which the increased release of new T-cells was accompanied by modifications of the T-cell repertoire. Glatiramer acetate modifies the peripheral T-cell pool by activating a thymopoietic pathway of T-cell release that leads to a different setting of T-cell diversity and, likely, to a dilution of autoreactive T-cells.

Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help

Blood ◽  
2005 ◽  
Vol 106 (6) ◽  
pp. 1924-1931 ◽  
Author(s):  
Svenja Hardtke ◽  
Lars Ohl ◽  
Reinhold Förster
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Helper Cells ◽  
Cell Area ◽  
T Helper ◽  
Helper Cells ◽  
Follicular T Helper Cells ◽  
Cell Follicle

Abstract The production of high-affinity antibodies to T-dependent antigens requires the interaction of B cells and T helper cells expressing receptors specific for the same antigen. Although several mechanisms have been elucidated that regulate B-cell trafficking within lymphoid organs, less is known about molecular cues that guide the small subpopulation of CD4+ follicular T helper cells to B-cell follicles. Using adoptive transfer of transgenic T cells in mice, we demonstrate that antigen-induced activation leads to a finely tuned positioning of T cells either to the T-cell area or the B-cell follicle. We show that expression of CXCR5 is indispensable for T cells to enter B-cell follicles, whereas expression of CCR7 provides a counteracting signal to retain activated T cells in the T-cell area. Although only few T cells transiently migrate from the T-cell area to the B-cell follicle of peripheral lymph nodes following antigenic challenge, this step is essential to provide the help B cells require to produce antibodies efficiently. Thus, we demonstrate that the balanced expression of CCR7 and CXCR5 determines the positioning and proper function of follicular T helper cells.

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