scholarly journals Evolution of the Primary Immune Response toHistoplasma capsulatum in Murine Lung

1998 ◽  
Vol 66 (4) ◽  
pp. 1473-1481 ◽  
Author(s):  
Judith A. Cain ◽  
George S. Deepe
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Interleukin 2 ◽  
Primary Immune Response ◽  
Pcr Analysis ◽  
Cell Populations ◽  
Mrna Levels ◽  
Cytoplasmic Staining ◽  
Inflammatory Reactions ◽  
Ifn Γ

ABSTRACT Histoplasma capsulatum induces a cell-mediated immune response in the lungs and lymphoid organs of mammals. In this study, we analyzed the progression of the cytokine and inflammatory reactions in the lungs of mice infected intranasally with H. capsulatum. We measured cytokine mRNA levels and determined the inflammatory cell populations during the active phase of infection (<3 weeks). Transcription of genes encoding interleukin-2 (IL-2), IL-4, and IL-12 and gamma interferon (IFN-γ) was detectable as early as day 3 of infection, whereas a signal for IL-10 was never observed. Competitive PCR analysis demonstrated that enhanced expression of IL-12 mRNA was observed by day 3 and that expression of mRNA for IL-2 and IFN-γ progressively increased from day 5 to day 10. All levels declined by day 14. Analysis of the inflammatory response revealed an initial elevation in myeloid cells (Mac-1+) and natural killer (NK) cells followed by a rise in T cells, predominantly CD4+cells. Since IFN-γ is a key factor in host defense, we performed cytoplasmic staining to determine the cell populations that produced this cytokine. The hierarchy of synthesis was CD4+ > CD8+ > NK cells. Thus, H. capsulatum provokes an orderly modulation of the inflammatory and cytokine responses in murine lungs.

scholarly journals Phenotypical and Functional Characteristics of Human Regulatory T Cells during Ex Vivo Maturation from CD4+ T Lymphocytes

2021 ◽  
Vol 11 (13) ◽  
pp. 5776
Author(s):  
Varvara G. Blinova ◽  
Natalia S. Novachly ◽  
Sofya N. Gippius ◽  
Abdullah Hilal ◽  
Yulia A. Gladilina ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Ex Vivo ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Inflammatory Reactions ◽  
Effector Cells ◽  
Cycle Regulation ◽  
Further Development

Regulatory T cells (Tregs) participate in the negative regulation of inflammatory reactions by suppressing effector cells. In a number of autoimmune disorders, the suppressive function and/or the number of Tregs is compromised. The lack of active functioning Tregs can be restored with adoptive transfer of expanded ex vivo autologous Tregs. In our study, we traced the differentiation and maturation of Tregs CD4+CD25+FoxP3+CD127low over 7 days of cultivation from initial CD4+ T cells under ex vivo conditions. The resulting ex vivo expanded cell population (eTregs) demonstrated the immune profile of Tregs with an increased capacity to suppress the proliferation of target effector cells. The expression of the FoxP3 gene was upregulated within the time of expansion and was associated with gradual demethylation in the promotor region of the T cell-specific demethylation region. Real-time RT-PCR analysis revealed changes in the expression profile of genes involved in cell cycle regulation. In addition to FOXP3, the cells displayed elevated mRNA levels of Ikaros zinc finger transcription factors and the main telomerase catalytic subunit hTERT. Alternative splicing of FoxP3, hTERT and IKZF family members was demonstrated to be involved in eTreg maturation. Our data indicate that expanded ex vivo eTregs develop a Treg-specific phenotype and functional suppressive activity. We suggest that eTregs are not just expanded but transformed cells with enhanced capacities of immune suppression. Our findings may influence further development of cell immunosuppressive therapy based on regulatory T cells.

scholarly journals TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2

2020 ◽  
Author(s):  
Yinfang Wang ◽  
Yingzhe Fan ◽  
Yitong Huang ◽  
Tao Du ◽  
Zongjun Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nk Cells ◽  
Interleukin 2 ◽  
A549 Cells ◽  
Endogenous Retrovirus ◽  
Alveolar Epithelial Cells ◽  
Cell Entry ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Ifn Γ

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous retrovirus latency and immune response, it is recently reported to be co-expressed with SARS-CoV-2 receptor in type II pneumocytes; however, the roles of TRIM28 in ACE2 expression and SARS-CoV-2 cell entry remain unclear. This study showed that knockdown of TRIM28 induces ACE2 expression and increases pseudotyped SARS-CoV-2 cell entry of A549 cells and primary pulmonary alveolar epithelial cells (PAEpiCs). In a co-culture model of NK cells and lung epithelial cells, our results demonstrated that NK cells inhibit TRIM28 and promote ACE2 expression in lung epithelial cells, which was partially reversed by depletion of interleukin-2 and blocking of granzyme B in the co-culture medium. Furthermore, TRIM28 knockdown enhanced interferon-γ (IFN-γ)-induced ACE2 expression through a mechanism involving upregulating IFN-γ receptor 2 (IFNGR2) in both A549 and PAEpiCs. Importantly, the upregulated ACE2 induced by TRIM28 knockdown and co-culture of NK cells was partially reversed by dexamethasone in A549 cells but not PAEpiCs. Our study identified TRIM28 as a novel regulator of ACE2 expression and SARS-CoV-2 cell entry.

scholarly journals Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells

2000 ◽  
Vol 74 (17) ◽  
pp. 7738-7744 ◽  
Author(s):  
Sangkon Oh ◽  
Maryna C. Eichelberger
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Interleukin 2 ◽  
Dependent Manner ◽  
Ifn Γ ◽  
High Doses ◽  
Type Response

ABSTRACT The developing immune response in the lymph nodes of mice infected with influenza virus has both Th1- and Th2-type characteristics. Modulation of the interactions between antigen-presenting cells and T cells is one mechanism that may alter the quality of the immune response. We have previously shown that the ability of dendritic cells (DC) to stimulate the proliferation of alloreactive T cells is changed by influenza virus due to viral neuraminidase (NA) activity. Here we show that DC infected with influenza virus A/PR/8/34 (PR8) stimulate T cells to produce different types of cytokines in a dose-dependent manner. Optimal amounts of the Th1-type cytokines interleukin-2 (IL-2) and gamma interferon (IFN-γ) were produced from T cells stimulated by DC infected with low doses of PR8, while the Th2-type cytokines IL-4 and IL-10 were produced only in response to DC infected with high doses of PR8. IL-2 and IFN-γ levels corresponded with T-cell proliferation and were dependent on the activity of viral NA on the DC surface. In contrast, IL-4 secretion required the treatment of T cells with NA. Since viral particles were released only from DC that are infected with high doses of PR8, our results suggest that viral NA on newly formed virus particles desialylates T-cell surface molecules to facilitate a Th2-type response. These results suggest that the activity of NA may contribute to the mixed Th-type response observed during influenza virus infection.

scholarly journals CMV-Specific Immune Response—New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation

2019 ◽  
Vol 20 (2) ◽  
pp. 271 ◽  
Author(s):  
Przemyslaw Zdziarski
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Cellular Immune Response ◽  
Specific Immune Response ◽  
Primary Immune Response ◽  
Virus Reactivation ◽  
Allogenic Stem Cell Transplantation ◽  
Specific Igg ◽  
Cellular Immune

Although the existing paradigm states that cytomegalovirus (CMV) reactivation is under the control of the cellular immune response, the role of humoral and innate counterparts are underestimated. The study analyzed the host–virus interaction i.e., CMV-immune response evolution during infection in three different clinical situations: (1) immunodeficient CMV-positive human leukocyte antigen (HLA)-matched bone marrow recipients after immunoablative conditioning as well as immunocompetent, (2) adult, and (3) infant with primary immune response. In the first situation, a fast and significant decrease of specific immunity was observed but reconstitution of marrow-derived B and natural killer (NK) cells was observed prior to thymic origin of T cells. The lowest CMV-IgG (93.2 RU/mL) was found just before CMV viremia. It is noteworthy that the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was detected later, but in the first phase, phytohemagglutinin (PHA)-induced IFN-γ release was significantly lower than that of CMV-induced (“indeterminate” results). It corresponds with the increase of NK cells at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells using a pentamer technique. In immunocompetent adult (CMV-negative donor), the cellular and humoral immune response increased in a parallel manner, but symptoms of CMV mononucleosis persisted until the increase of specific IgG. During infancy, the decrease of the maternal CMV-IgG level to 89.08 RU/mL followed by clinical sequel, i.e., CMV replication, were described. My observations shed light on a unique host-CMV interaction and CMV-IgG role: they indicate that its significant decrease predicts CMV replication. Before primary cellular immune response development, the high level of residual CMV-IgG (about >100 R/mL) from mother or recipient prevents virus reactivation. The innate immune response and NK-dependent IFN-secretion should be further investigated.

scholarly journals Stem Cell Factor Enhances Interleukin-2–Mediated Expansion of Murine Natural Killer Cells In Vivo

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3647-3653 ◽  
Author(s):  
Todd A. Fehniger ◽  
William E. Carson ◽  
Ewa Mrózek ◽  
Michael A. Caligiuri
Keyword(s):  
Nk Cells ◽  
Cell Expansion ◽  
Stem Cell Factor ◽  
Low Dose ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Innate Immune ◽  
Ifn Γ

Abstract The administration of low dose interleukin-2 (IL-2) results in a selective expansion of natural killer (NK) cells in vivo, and promotes the differentiation of NK cells from hematopoietic precursor cells in vitro. We have previously shown that stem cell factor (SCF ), the ligand to the c-kit tyrosine kinase receptor, enhances IL-2–induced NK cell proliferation and differentiation in vitro. Here, we investigated the effects of SCF plus IL-2 delivered to mice in vivo. Eight-week-old C57BL/6 mice were treated with a continuous subcutaneous infusion of IL-2 (1 × 104 IU/d) plus a daily intraperitoneal dose of SCF (100 μg/kg/d), IL-2 alone, SCF alone, or vehicle alone for 8 weeks. The in vivo serum concentration of IL-2 ranged between 352 ± 12.0 pg/mL and 606 ± 9.0 pg/mL, achieving selective saturation of the high affinity IL-2 receptor, while the peak SCF serum concentration was 296 ± 13.09 ng/mL. Alone, the daily administration of SCF had no effect on the expansion of NK cells. The continuous infusion of IL-2 alone did result in a significant expansion of NK1.1+CD3− cells compared to mice treated with placebo or SCF. However, mice treated with both SCF and IL-2 showed an increase in the absolute number of NK cells that was more than twofold that seen with IL-2 alone, in the spleen (P ≤ .005), bone marrow (P ≤ .025), and blood (P < .05). NK cytotoxic activity against YAC-1 target cells was significantly higher for mice treated with SCF plus IL-2, compared to mice treated with IL-2 alone (P ≤ .0005). Interferon-γ (IFN-γ) production in cytokine-activated splenocytes was also greater for the SCF plus IL-2 group, over IL-2 treatment alone (P ≤ .01). The effect of SCF plus IL-2 on NK cell expansion was likely mediated via NK cell precursors, rather than mature NK cells. In summary, we provide the first evidence that SCF can significantly enhance expansion of functional NK cells induced by the prolonged administration of low dose IL-2 in vivo. Since the NK cell is a cytotoxic innate immune effector and a potent source of IFN-γ, this therapeutic strategy for NK cell expansion may serve to further enhance innate immune surveillance against malignant transformation and infection in the setting of cancer and/or immunodeficiency.

scholarly journals Angiogenic Growth Factor Messenger Ribonucleic Acids in Uterine Natural Killer Cells1

2001 ◽  
Vol 86 (4) ◽  
pp. 1823-1834 ◽  
Author(s):  
Xiao Feng Li ◽  
D. Stephen Charnock-Jones ◽  
Eko Zhang ◽  
Susan Hiby ◽  
Shazia Malik ◽  
...  
Keyword(s):  
Growth Factor ◽  
Nk Cells ◽  
Interleukin 2 ◽  
Human Endometrium ◽  
Mrna Levels ◽  
Angiogenic Growth Factors ◽  
Secretory Phase ◽  
Killer Cells ◽  
Ribonucleic Acids ◽  
Wide Range

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.

scholarly journals Predominance of Th1 Immune Response in Pleural Effusion of Patients with Tuberculosis among Other Exudative Etiologies

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Vinícius da Cunha Lisboa ◽  
Marcelo Ribeiro-Alves ◽  
Raquel da Silva Corrêa ◽  
Isabelle Ramos Lopes ◽  
Thiago Thomaz Mafort ◽  
...  
Keyword(s):  
Immune Response ◽  
Pleural Effusion ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Principal Component ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Biochemical Tests ◽  
Cross Sectional ◽  
Ifn Γ

ABSTRACT Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically confirmed or not) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB) (n = 25) patients. The levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, IFN-γ, tumor necrosis factor (TNF), IP-10, transforming growth factor β1 (TGF-β), and ADA were determined using cytometric bead assay, enzyme-linked immunosorbent assay (ELISA), or biochemical tests. IFN-γ, IP-10, TNF, TGF-β, and ADA quantified in PF showed significantly higher concentrations in PlTB patients than in nTB patients. When blood and PF were compared, significantly higher concentrations of IL-6 and IL-10 in PF were identified in both groups. TGF-β, solely, showed significantly increased levels in PF and blood from PlTB patients when both clinical specimens were compared to those from nTB patients. Principal-component analysis (PCA) revealed a T helper type 1 (Th1) pattern attributed mainly to higher levels of IP-10, IFN-γ, TGF-β, and TNF in the pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases, rather than other causes of exudative effusion commonly considered in the differential diagnosis of PlTB.

scholarly journals Characterization of Avian γδ T-Cell Subsets afterSalmonella entericaSerovar Typhimurium Infection of Chicks

2010 ◽  
Vol 79 (2) ◽  
pp. 822-829 ◽  
Author(s):  
Jana Pieper ◽  
Ulrich Methner ◽  
Angela Berndt
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Fas Ligand ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Immune Defense ◽  
T Cell Subsets ◽  
Mrna Levels ◽  
Γδ T Cell ◽  
Ifn Γ

ABSTRACTAvian γδ T lymphocytes are frequently found in blood and organs and are assumed to be crucial to the immune defense againstSalmonellainfections of chicks. To elucidate the so-far-unknown immunological features of subpopulations of avian γδ T cells in the course of infection, day-old chicks were infected orally withSalmonella entericaserovar Typhimurium. Until 11 days after infection, the occurrence as well as transcription of the CD8 antigen and immunologically relevant protein genes of CD8α−and CD8α+high(CD8αα+CD8αβ+) γδ cells were analyzed using flow cytometry and quantitative real-time reverse transcription-PCR (RT-PCR) with blood, spleen, thymus, and cecum samples. After infection, an increased percentage of CD8α+highγδ T lymphocytes was found in blood, in spleen, and, with the highest values and most rapidly, in cecum. Within the CD8α+highsubset, a significant rise in the number of CD8αα+cells was accompanied by enhanced CD8α antigen expression and reduced gene transcription of the CD8β chain. CD8αα+and CD8αβ+cells showed elevated transcription for Fas, Fas ligand (FasL), interleukin-2 receptor α (IL-2Rα), and gamma interferon (IFN-γ). While the highest fold changes in mRNA levels were observed in CD8αβ+cells, the mRNA expression rates of CD8αβ+cells never significantly exceeded those of the CD8αα+cells. In conclusion, both CD8α+highγδ T-cell subpopulations (CD8αα+and CD8αβ+) might be a potential source of IFN-γ inSalmonella-infected chicks. However, due to their prominent frequency in blood and organs after infection, the avian CD8αα+γδ T-cell subset seems to be unique and of importance in the course ofSalmonellaTyphimurium infection of very young chicks.

Dual function for the adaptor MIST in IFN-γ production by NK and CD4+NKT cells regulated by the Src kinase Fgr

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3647-3655 ◽  
Author(s):  
Hiroki Sasanuma ◽  
Akiko Tatsuno ◽  
Shinya Hidano ◽  
Keiko Ohshima ◽  
Yumi Matsuzaki ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Cell Receptor ◽  
Nkt Cells ◽  
Cell Populations ◽  
Dual Function ◽  
Ifn Γ ◽  
Nk Cell Receptor

Natural killer (NK) cells and NKT cells play critical early roles in host defense. Here we show that MIST, an adaptor protein belonging to the SLP-76 family, functions negatively in NK cells but positively in CD4+NKT cells. NK-cell receptor-mediated IFN-γ production was enhanced in NK cells, whereas TCR- or NK-cell receptor-mediated cytokine production was reduced in CD4+NKT cells from MIST-deficient mice. These opposite effects of MIST paralleled the exclusive expression of the Src family kinase, Fgr, in NK cells between the 2 cell populations. We further demonstrated that interaction of MIST with Fgr, mediated by the C-terminal proline-rich region of MIST and the SH3 domain of Fgr, was required for the suppression of NK-cell receptor-induced IFN-γ production. This functional interdependence of signaling molecules demonstrates a new mechanism by which adaptor proteins can act as molecular switches to control diverse responses in different cell populations.

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