scholarly journals Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

AGE ◽  
2013 ◽  
Vol 36 (2) ◽  
pp. 571-582 ◽  
Author(s):  
Malin Bengnér ◽  
Vivien Béziat ◽  
Jan Ernerudh ◽  
Bengt-Olof Nilsson ◽  
Sture Löfgren ◽  
...  
Keyword(s):  
T Cell ◽  
Division Of Labor ◽  
Adaptive Immunity ◽  
Cytomegalovirus Infection ◽  
Nk Cell ◽  
Innate And Adaptive Immunity ◽  
Cell Compartments

Targeting CD137 to enhance the antitumor efficacy of cetuximab by stimulation of innate and adaptive immunity.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3015-3015 ◽  
Author(s):  
Holbrook Edwin Kohrt ◽  
Roch Houot ◽  
Kipp Weiskopf ◽  
Matthew Goldstein ◽  
Peder Lund ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Cell Depletion ◽  
Innate And Adaptive Immunity ◽  
Cetuximab Therapy

3015 Background: Cetuximab therapy results in beneficial, yet limited, clinical improvement for patients with KRAS wildtype (WT) colorectal (CRC) and head and neck (HN) cancer. The efficacy of cetuximab, an IgG1 monoclonal antibody against EGFR, is due in part to antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells. CD137 is a costimulatory molecule expressed following activation on NK and memory, antigen-specific, CD8 T cells. Methods: We investigated the hypothesis that the combination of cetuximab with anti-CD137 mAb will enhance innate and adaptive immunity, thereby improving cetuximab’s anti-tumor efficacy in preclinical models and a prospective trial, NCT01114256. Results: NK cells increased their expression of CD137 by a factor of 30-40 when exposed to cetuximab-coated, EGFR-expressing HN and CRC cell lines. An agonistic anti-CD137 mAb enhanced NK cell degranulation and cytotoxicity 2-fold (~45 to 90% tumor lysis assayed by chromium release). The combination of cetuximab and anti-CD137 mAbs was synergistic in a syngeneic, human-EGFR-transfected murine tumor leading to complete tumor resolution and prolonged survival. NK cell depletion, significantly, and CD8 T cell depletion, partly, abrogated the anti-tumor efficacy of this combination. A series of HN and both KRAS WT and mutant CRC xenotransplant models demonstrated synergy with cetuximab and anti-CD137 mAbs. In our clinical trial, 54 patients with HN cancer receiving cetuximab therapy, circulating and intratumoral NK cells upregulated CD137 with amplitude influenced by duration post-cetuximab and host FcyRIIIa polymorphism. Interestingly, in 10 HLA-A2+ patients, following cetuximab, an increase in EGFR-specific, CD137-expressing, CD8 T cells directly correlated with the percent increase in CD137-expressing NK cells. Conclusions: Our results demonstrate the synergy of combining an agonistic mAb, anti-CD137, augmenting ADCC and T cell memory following a tumor-targeting mAb, cetuximab, in HN and KRAS mutant and WT CRC cancer. These results support a novel, sequential antibody approach by targeting first the tumor and then the host innate and adaptive immune system. Clinical trial information: NCT01114256.

Introduction to Clinical Immunology: Overview of the Immune Response, Autoimmune Conditions, and Immunosuppressive Therapeutics for Rheumatic Diseases

2016 ◽  
Author(s):  
Steven K. Lundy ◽  
Alison Gizinski ◽  
David A. Fox
Keyword(s):  
Immune Response ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Cell Populations ◽  
Hematopoietic Stem ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune

The immune system is a complex network of cells and mediators that must balance the task of protecting the host from invasive threats. From a clinical perspective, many diseases and conditions have an obvious link to improper functioning of the immune system, and insufficient immune responses can lead to uncontrolled acute and chronic infections. The immune system may also be important in tumor surveillance and control, cardiovascular disease, health complications related to obesity, neuromuscular diseases, depression, and dementia. Thus, a working knowledge of the role of immunity in disease processes is becoming increasingly important in almost all aspects of clinical practice. This review provides an overview of the immune response and discusses immune cell populations and major branches of immunity, compartmentalization and specialized immune niches, antigen recognition in innate and adaptive immunity, immune tolerance toward self antigens, inflammation and innate immune responses, adaptive immune responses and helper T (Th) cell subsets, components of the immune response that are important targets of treatment in autoimmune diseases, mechanisms of action of biologics used to treat autoimmune diseases and their approved uses, and mechanisms of other drugs commonly used in the treatment of autoimmune diseases. Figures show the development of erythrocytes, platelets, lymphocytes, and other immune system cells originating from hematopoietic stem cells that first reside in the fetal liver and later migrate to the bone marrow, antigen–major histocompatibility complex recognition by T cell receptor control of T cell survival and activation, and Th cells as central determinants of the adaptive immune response toward different stimuli. Tables list cell populations involved in innate and adaptive immunity, pattern recognition receptors with known ligands, autoantibody-mediated human diseases: examples of pathogenic mechanisms, selected Food and Drug Administration–approved autoimmune disease indications for biologics, and mechanism of action of biologics used to treat autoimmune diseases.   This review contains 3 highly rendered figures, 5 tables, and 64 references.

Primary infection with simian immunodeficiency virus: plasmacytoid dendritic cell homing to lymph nodes, type I interferon, and immune suppression

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4598-4608 ◽  
Author(s):  
Benoît Malleret ◽  
Benjamin Manéglier ◽  
Ingrid Karlsson ◽  
Pierre Lebon ◽  
Michelina Nascimbeni ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Adaptive Immunity ◽  
Immune Suppression ◽  
Primary Infection ◽  
Type I Interferon ◽  
Type I ◽  
Innate And Adaptive Immunity ◽  
Immunodeficiency Virus

AbstractPlasmacytoid dendritic cells (pDCs) are antigen-presenting cells that develop into type-I interferon (IFN-I)–producing cells in response to pathogens. Their role in human immunodeficiency virus (HIV) pathogenesis needs to be understood. We analyzed their dynamics in relation to innate and adaptive immunity very early during the acute phase of simian immunodeficiency virus (SIV) infection in 18 macaques. pDC counts decreased in blood and increased in peripheral lymph nodes, consistent with early recruitment in secondary lymphoid tissues. These changes correlated with the kinetic and intensity of viremia and were associated with a peak of plasma IFN-I. IFN-I and viremia were positively correlated with functional activity of the immune suppression associated enzyme indoleamine-2,3-dioxygenase (IDO) and FoxP3+CD8+ T cells, which both negatively correlated with SIV-specific T-cell proliferation and CD4+ T-cell activation. These data suggest that pDCs and IFN-I play a key role in shaping innate and adaptive immunity toward suppressive pathways during the acute phase of SIV/HIV primary infection.

Rapid Reconstitution of Human Antibody Secreting Cells After Haploidentical Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3682-3682
Author(s):  
Martina Steurer ◽  
Elke Malenke ◽  
Birgit Federmann ◽  
Lothar Kanz ◽  
Wolfgang Andreas Bethge ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
T Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Adaptive Immunity ◽  
Cell Transplantation ◽  
Innate And Adaptive Immunity ◽  
Antibody Secreting Cells

Abstract Abstract 3682 Poster Board III-618 Innate immunity including granulocytes, monocytes, and NK cells is reported to recover rapidly after allogeneic stem cell transplantation within weeks. In contrast, adaptive immunity, including T- and B-cells, has delayed recovery over months. In murine models innate type marginal zone and B1 B cells, established at fetal age and providing natural antibodies, are distinguished from adaptive B2 or follicular B cells. A crucial maturation and survival factor for adaptive murine B cells was shown to be TNF-family member BAFF (B cell-activating factor), while development of innate B1 B cells is BAFF independent. Kinetics in reconstitution of innate and adaptive immunity after ablation in adults may give insight into hierarchy and attribution to innate and adaptive immunity of defined lymphocyte populations. Reconstitution of lymphopoiesis after CD3 and CD19 depleted haploidentical stem cell transplantation was analyzed in 10 patients, which received monoclonal anti-CD3 antibody OKT3 as immunosuppressant only. This model may enable detailed in vivo evaluation of de novo B cell formation. Weekly samples before and after reduced-intensity conditioning were analyzed by flow cytometry for absolute numbers of T-cell, NK-, and B-cell subsets. Their origin of host or donor hematopoiesis was differentiated by HLA-FACS. Antibody secreting cells (ASC) were enumerated by ELISPOT. Plasma cytokine concentrations were determined by bead based arrays and ELISA. Complete reconstitution of allogeneic NK cells was found at day +21 after transplantation. CD4+ and CD8+ T-cells and their subsets had delayed reconstitution with less then 100 cells/μl at 3 months after transplantation. CD19+ B-lymphocytes of naïve and memory phenotype (>0,5% of all lymphocytes) were detected not before day +60. In contrast, complete reconstitution of antibody-secreting cells after a nadir (<0,05/μl) was observed at day +14. Absolute numbers of ASC were comparable to those of healthy controls (d+14: 72 ASC/μl vs. control: 12 ASC/μl). ASC secreting the isotypes IgM and IgA were more prevalent than IgG compared to controls (time increase: IgM 20; IgA 10; IgG 2,9). These ASC appear CD19low/neg, CD38+, and intracellular Ig+ in flow cytometry and carried donor HLA-haplotype. Reconstitution of ASC occurred without detectable circulating T-cells and before increase of BAFF concentrations were observed. In summary, the rapid and complete reconstitution of peripheral blood ASC after allogeneic transplantation, far proceeding detection of naïve and memory type B-cells, is a novel observation. Incidence before T-cell reconstitution and increase in BAFF concentrations indicates a T-cell and BAFF independent mechanism allocating these early ASC to innate immunity, potentially maintaining natural antibody levels. Disclosures: No relevant conflicts of interest to declare.

The specific NK cell response in concert with perforin prevents CD8+ T cell-mediated immunopathology after mouse cytomegalovirus infection

2015 ◽  
Vol 204 (3) ◽  
pp. 335-344 ◽  
Author(s):  
Jurica Arapović ◽  
Maja Arapović ◽  
Mijo Golemac ◽  
Luka Traven ◽  
Jelena Tomac ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Cytomegalovirus Infection ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Mouse Cytomegalovirus

scholarly journals CD1-Restricted T Cells at the Crossroad of Innate and Adaptive Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Catia S. Pereira ◽  
M. Fatima Macedo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adaptive Immunity ◽  
Mhc Class I ◽  
Structural Features ◽  
Class I ◽  
Innate And Adaptive Immunity ◽  
Lipid Antigens ◽  
Different Types ◽  
Antigen Presenting

Lipid-specific T cells comprise a group of T cells that recognize lipids bound to the MHC class I-like CD1 molecules. There are four isoforms of CD1 that are expressed at the surface of antigen presenting cells and therefore capable of presenting lipid antigens: CD1a, CD1b, CD1c, and CD1d. Each one of these isoforms has distinct structural features and cellular localizations, which promotes binding to a broad range of different types of lipids. Lipid antigens originate from either self-tissues or foreign sources, such as bacteria, fungus, or plants and their recognition by CD1-restricted T cells has important implications in infection but also in cancer and autoimmunity. In this review, we describe the characteristics of CD1 molecules and CD1-restricted lipid-specific T cells, highlighting the innate-like and adaptive-like features of different CD1-restricted T cell subtypes.

scholarly journals FACTORS OF CONGENITAL AND ADAPTIVE IMMUNITY IN THE PATHOGENESIS OF INTRAUTERINE GENERATED CYTOMEGALOVIRUS INFECTION

2021 ◽  
Vol 23 (4) ◽  
pp. 799-804
Author(s):  
M. A. Levkovich ◽  
L. V. Kravchenko ◽  
A. A. Afonin ◽  
I. I. Krukier ◽  
A. Yu. Levkovich ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Cytomegalovirus Infection ◽  
Clinical Symptoms ◽  
Control Group ◽  
Antiviral Immune Response ◽  
Innate And Adaptive Immunity ◽  
Group I ◽  
Severity Of The Disease

Subject: to assess a role of factors of innate and adaptive immunity in the development of intrauterine generalized cytomegalovirus infection.The study included 47 newborns with congenital generalized cytomegalovirus infection comprising group I. Based on the data of clinical and laboratory examination, all newborns studied were divided into two subgroups. Subgroup 1.1 (29 subjects) consisted of newborns with severe CMVI and subgroup 1.2 (18 subjects) – newborns with moderate CMVI. The control group included 26 newborns without herpesvirus infection.Determination of the number of monocytes expressing Toll receptors (TLR) was performed by laser flow cytometry (Beckman Coulter) using Beckman Coulter, HyCultBiotechnology reagents: FITC-CD282+, CD284+, CD286+, and PE-CD14+. The newborn serum concentration of IFNγ, IFNα, IL-6, IL-8 was determined by ELISA using BenderMedsistems test systems.Intrauterine generalized CMVI with complete clinical symptoms in newborns was characterized by a decrease in the number of monocytes expressing TLR-2 and TLR-6, which was associated with a decrease in the level of IFNα, IFNγ, an increase in the level of IL-6, IL-8 and MCP-1. The subgroup with incomplete clinical symptoms CMVI was characterized by a decrease in the level of IFNα, in combination with an increase in the level of IL-6. The identified immune disorders lead to a reduction in the antiviral immune response and determine the severity of the disease in prenatally infected newborns. 

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