scholarly journals THE ROLE OF CD200/CD200R INTERACTIONS IN THE FORMATION OF IMMUNOLOGICAL TOLERANCE IN TRANSPLANTATION AND PREGNANCY

2018 ◽  
Vol 20 (6) ◽  
pp. 807-814
Author(s):  
A. S. Arefieva ◽  
A. A. Babayan ◽  
E. O. Stepanova ◽  
T. V. Dontsova ◽  
S. V. Pavlovich ◽  
...  
Keyword(s):  
T Cells ◽  
Spontaneous Abortion ◽  
Cell Types ◽  
Immunological Tolerance ◽  
Lymphoid Cells ◽  
Autoimmune Processes ◽  
Transplanted Organs

The transmembrane CD200 glycoprotein belongs to the immunoglobulin family and it is widely represented on a variety of cell types, while its structurally similar CD200R receptor is expressed, mainly, on myeloid and lymphoid cells. An immunomodulatory role of CD200 and CD200R interaction is to activate the intracellular inhibitory cascade of reactions, leading to suppression of effector immune cells and attenuation of the inflammatory process. Thus, the CD200R activation stimulates the differentiation of naive T cells to regulatory T cells, increasing the indolamine 2,3-dioxygenase activity, and enhances the synthesis of IL-10 and TGF-β cytokines, contributing to development of a Th2-dependent anti-inflammatory environment. These immune regulatory events provide the development of immune tolerance and are required for controlling the development of autoimmune processes, hypersensitivity, engraftment of transplanted organs and tissues, as well as protecting the fetus from spontaneous abortion. Tolerogenic potential of interaction between CD200 and CD200R molecules can be effectively used for treatment of various diseases (e.g., Alzheimer’s, rheumatoid arthritis, allergies). In this review, we will address the role of CD200/CD200R interactions in stimulating the post-transplant engraftment and protecting a fetus from spontaneous abortion. Many in vivo and in vitro studies have suggested a key role of CD200/CD200R interaction in immune maintenance of both processes. 

scholarly journals The critical immunosuppressive effect of MDSC-derived exosomes in the tumor microenvironment

2020 ◽  
Author(s):  
Mohammad H. Rashid ◽  
Thaiz F. Borin ◽  
Roxan Ara ◽  
Raziye Piranlioglu ◽  
Bhagelu R. Achyut ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Biological Macromolecules

AbstractMyeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME), and our perception regarding the role of MDSCs in tumor promotion is attaining extra layer of intricacy in every study. In conjunction with MDSC’s immunosuppressive and anti-tumor immunity, they candidly facilitate tumor growth, differentiation, and metastasis in several ways that yet to be explored. Alike any other cell types, MDSCs also release a tremendous amount of exosomes or nanovesicles of endosomal origin and partake in intercellular communications by dispatching biological macromolecules. There has not been any experimental study done to characterize the role of MDSCs derived exosomes (MDSC exo) in the modulation of TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant amount of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those are in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating the mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that immunosuppressive and tumor-promoting functions of MDSC are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.

scholarly journals The role of H-2-linked genes in helper T-cell function. III. Expression of immune response genes for trinitrophenyl conjugates of poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in B cells and macrophages.

1978 ◽  
Vol 147 (6) ◽  
pp. 1596-1610 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Function ◽  
Cell Types ◽  
High Responder ◽  
In Vitro Response ◽  
Low Responder

Using lymph node T cells from poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys[(TG)-A--L]-primed animals and B cells from animals primed with trinitrophenylated (TNP) protein or lipopolysaccharide, we have obtained anti-TNP-(TG)-A--L direct plaque-forming responses in vitro. Response to this antigen was shown to be controlled by the H-2 haplotype of the animal studied. The strain distribution of in vitro response was very similar to that previously reported by others for in vivo secondary IgG responses to (TG)-A--L. We investigated the cell types expressing the Ir gene(s) for (TG)-A--L in our cultures. F1, high responder x low responder mice were primed with (TG)-A--L. Their T cells were active in stimulating anti-TNP-(TG)-A--L responses of high responder but not low responder B cells and macrophages (MPHI), even though both preparations of B cells and Mphi were obtained from mice congenic at H-2 with one of the parents of the F1. For three low responder strains tested, of the H-2h2, H-2k, and H-2f haplotypes, the anti-TNP-(TG)-A--L response of low responder B cells and Mphis in the presence of high responder, F1 T cells could not be improved by the addition of high responder, antigen-bearing Mphis to the cultures. In one strain of the H-2a haplotype, it was shown that neither the B cells nor Mphis could be functional in anti-TNP-(TG)-A--L responses. Our results therefore suggested the Ir genes for anti-TNP-(TG)-A--L responses were expressed at least in B cells in all the low responder strains we studied, and, in mice of the H-2a haplotype, in Mphis too.

scholarly journals Gastric Hyperplasia and Increased Proliferative Responses of Lymphocytes in Mice Lacking the COOH-terminal Ankyrin Domain of NF-κB2

1997 ◽  
Vol 186 (7) ◽  
pp. 999-1014 ◽  
Author(s):  
Hideaki Ishikawa ◽  
Daniel Carrasco ◽  
Estefania Claudio ◽  
Rolf-Peter Ryseck ◽  
Rodrigo Bravo
Keyword(s):  
T Cells ◽  
Lymphocyte Proliferation ◽  
Cytokine Production ◽  
Cell Types ◽  
Homozygous Deletion ◽  
Binding Activity ◽  
Activated T Cells ◽  
Physiological Relevance

The nfkb2 gene encodes the p100 precursor which produces the p52 protein after proteolytic cleavage of its COOH-terminal domain. Although the p52 product can act as an alternative subunit of NF-κB, the p100 precursor is believed to function as an inhibitor of Rel/NF-κB activity by cytoplasmic retention of Rel/NF-κB complexes, like other members of the IκB family. However, the physiological relevance of the p100 precursor as an IκB molecule has not been understood. To assess the role of the precursor in vivo, we generated, by gene targeting, mice lacking p100 but still containing a functional p52 protein. Mice with a homozygous deletion of the COOH-terminal ankyrin repeats of NF-κB2 (p100−/−) had marked gastric hyperplasia, resulting in early postnatal death. p100−/− animals also presented histopathological alterations of hematopoietic tissues, enlarged lymph nodes, increased lymphocyte proliferation in response to several stimuli, and enhanced cytokine production in activated T cells. Dramatic induction of nuclear κB–binding activity composed of p52-containing complexes was found in all tissues examined and also in stimulated lymphocytes. Thus, the p100 precursor is essential for the proper regulation of p52-containing Rel/NF-κB complexes in various cell types and its absence cannot be efficiently compensated for by other IκB proteins.

scholarly journals In Vivo Role of Dendritic Cells in a Murine Model of Pulmonary Cryptococcosis

2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Mouse Lung

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

Expression of CD10 by Human T Cells That Undergo Apoptosis Both In Vitro and In Vivo

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 3067-3076 ◽  
Author(s):  
Giovanna Cutrona ◽  
Nicolò Leanza ◽  
Massimo Ulivi ◽  
Giovanni Melioli ◽  
Vito L. Burgio ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Lymphoid Cells ◽  
Normal Peripheral Blood ◽  
Apoptotic Process ◽  
Cd10 Expression ◽  
T Cell Lines

Abstract This study shows that human postthymic T cells express CD10 when undergoing apoptosis, irrespective of the signal responsible for initiating the apoptotic process. Cells from continuous T-cell lines did not normally express CD10, but became CD10+ when induced into apoptosis by human immunodeficiency virus (HIV) infection and exposure to CD95 monoclonal antibody, etoposide, or staurosporin. Inhibitors of caspases blocked apoptosis and CD10 expression. Both CD4+ and CD8+ T cells purified from normal peripheral blood expressed CD10 on apoptotic induction. CD10 was newly synthesized by the apoptosing cells because its expression was inhibited by exposure to cycloheximide and CD10 mRNA became detectable by reverse transcription-polymerase chain reaction in T cells cultured under conditions favoring apoptosis. To show CD10 on T cells apoptosing in vivo, lymph node and peripheral blood T cells from HIV+ subjects were used. These suspensions were composed of a substantial, although variable, proportion of apoptosing T cells that consistently expressed CD10. In contrast, CD10+ as well as spontaneously apoptosing T cells were virtually absent in peripheral blood from normal individuals. Collectively, these observations indicate that CD10 may represent a reliable marker for identifying and isolating apoptosing T cells in vitro and ex vivo and possibly suggest novel functions for surface CD10 in the apoptotic process of lymphoid cells.

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

scholarly journals Signaling function of PRC2 is essential for TCR-driven T cell responses

2018 ◽  
Vol 215 (4) ◽  
pp. 1101-1113 ◽  
Author(s):  
Marc-Werner Dobenecker ◽  
Joon Seok Park ◽  
Jonas Marcello ◽  
Michael T. McCabe ◽  
Richard Gregory ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Polycomb Repressive Complex 2 ◽  
Histone Lysine Methyltransferases

Differentiation and activation of T cells require the activity of numerous histone lysine methyltransferases (HMT) that control the transcriptional T cell output. One of the most potent regulators of T cell differentiation is the HMT Ezh2. Ezh2 is a key enzymatic component of polycomb repressive complex 2 (PRC2), which silences gene expression by histone H3 di/tri-methylation at lysine 27. Surprisingly, in many cell types, including T cells, Ezh2 is localized in both the nucleus and the cytosol. Here we show the presence of a nuclear-like PRC2 complex in T cell cytosol and demonstrate a role of cytosolic PRC2 in T cell antigen receptor (TCR)–mediated signaling. We show that short-term suppression of PRC2 precludes TCR-driven T cell activation in vitro. We also demonstrate that pharmacological inhibition of PRC2 in vivo greatly attenuates the severe T cell–driven autoimmunity caused by regulatory T cell depletion. Our data reveal cytoplasmic PRC2 is one of the most potent regulators of T cell activation and point toward the therapeutic potential of PRC2 inhibitors for the treatment of T cell–driven autoimmune diseases.

scholarly journals Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection.

1994 ◽  
Vol 180 (4) ◽  
pp. 1273-1282 ◽  
Author(s):  
M B Graham ◽  
V L Braciale ◽  
T J Braciale
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Lymphocytes ◽  
Cd4 T Cells ◽  
Primary Role ◽  
T Helper ◽  
Helper Type

T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our studies have revealed that Th1 clones are cytolytic in vitro and protective against lethal challenge with virus in vivo, whereas Th2 clones are noncytolytic and not protective. Upon further evaluation of these clonal populations we have shown that not only are the Th2 clones nonprotective, but that pulmonary pathology is exacerbated as compared with control mice as evidenced by delayed viral clearance and massive pulmonary eosinophilia. These data suggest that virus-specific CD4+ T cells of the Th2 subset may not play a primary role in virus clearance and recovery and may lead to immune mediated potentiation of injury.

Mechanisms of IL-21 Enhancement of Rituximab Efficacy in a Lymphoma Xenograft Model.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1404-1404
Author(s):  
Steve D. Hughes ◽  
Ken Bannink ◽  
Cecile Krejsa ◽  
Mark Heipel ◽  
Becky Johnson ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Nk Cell ◽  
Antibody Therapy ◽  
Xenograft Model ◽  
Tumor Model ◽  
Cell Types ◽  
Current Evidence

Abstract Interleukin 21 (IL-21) is an IL-2 family cytokine produced by activated CD4+ T cells. Potent effects of IL-21 have been observed on the growth, survival, and functional activation of T cells, B cells, and natural killer (NK) cells. A Phase I clinical trial of IL-21 in metastatic melanoma and renal cell carcinoma is currently in progress. We recently reported that IL-21 significantly enhanced rituximab mediated clearance of CD20+ lymphoma cell lines both in vitro and in vivo, and that these effects were potentially mediated through IL-21 enhancement of NK cell capacity to effect antibody dependent cellular cytotoxicity (ADCC). Specifically, NK cells treated with IL-21 showed increased cytotoxicity, granzyme B and IFNg production. Current studies aim to further evaluate the mechanisms by which IL-21 enhances ADCC. A number of observations suggest a multi-factorial basis for IL-21 synergy with rituximab. In a xenograft tumor model, SCID mice were injected IV with HS Sultan cells on day 0. Treatment with recombinant murine IL-21 (mIL-21; starting day 1) combined with rituximab (starting day 3) resulted in significantly increased survival (70% vs. 20% on day 100), compared to rituximab alone. In separate studies, the spleens of mice treated with mIL-21 showed increased numbers of activated macrophages and granulocytes. As macrophages and granulocytes can participate in ADCC, IL-21 synergy with rituximab in vivo may be partly dependent on its activation of these cell types. We have also evaluated whether direct effects of IL-21 on lymphoma cells contribute to enhancement of rituximab efficacy. The xenogeneic B lymphoma models in which IL-21 plus rituximab exhibited enhanced survival are highly aggressive and these models were not shown to respond to treatment with mIL-21 alone. In vitro studies were performed to determine if IL-21 could potentiate the growth inhibitory and pro-apoptotic effects of rituximab. In the absence of effector cells synergistic interaction was not observed. In addition, we tested the ability of IL-21 to enhance cytotoxicity when combined with antibodies targeting non-hematopoietic tumor cells (e.g. trastuzumab). Human NK cells treated with IL-21 displayed significantly increased cytotoxicity in ADCC assays using trastuzumab to target breast cancer cells expressing varying levels of HER-2 antigen. In summary, the current evidence suggests that IL-21 can enhance antibody-mediated tumor cell lysis through activation of multiple effectors of ADCC. Thus IL-21 may prove to be broadly applicable to monoclonal antibody therapy of cancer.

Sign in / Sign up

Export Citation Format

Share Document