NK Cell Development in Human Immune System (HIS) Mice and Their Role in HIV Pathogenesis

2014 ◽  
pp. 161-179
Author(s):  
Yan Li ◽  
Silvia Lopez-Lastra ◽  
Guillemette X. Masse ◽  
James P. Di Santo
Keyword(s):  
Immune System ◽  
Nk Cell ◽  
Cell Development ◽  
Human Immune System ◽  
Hiv Pathogenesis ◽  
Human Immune

scholarly journals Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence

Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4158-4167 ◽  
Author(s):  
Till Strowig ◽  
Obinna Chijioke ◽  
Paolo Carrega ◽  
Frida Arrey ◽  
Sonja Meixlsperger ◽  
...  
Keyword(s):  
Immune System ◽  
Cord Blood ◽  
Nk Cells ◽  
Nk Cell ◽  
Human Immune System ◽  
Hematopoietic Progenitor ◽  
Human Adult ◽  
System Components ◽  
Human Immune

Abstract To investigate human natural killer (NK)–cell reactivity in vivo we have reconstituted human immune system components by transplantation of human hematopoietic progenitor cells into NOD-scid IL2Rγnull mice. We demonstrate here that this model allows the development of all NK-cell subsets that are also found in human adult peripheral and cord blood, including NKp46+CD56− NK cells. Similar to human cord blood, NK cells from these reconstituted mice require preactivation by interleukin-15 to reach the functional competence of human adult NK cells. Mainly the terminally differentiated CD16+ NK cells demonstrate lower reactivity without this stimulation. After preactivation, both CD16+ and CD16− NK cells efficiently produce interferon-γ and degranulate in response to stimulation with NK cell–susceptible targets, including K562 erythroleukemia cells. NK-cell lines, established from reconstituted mice, demonstrate cytotoxicity against this tumor cell line. Importantly, preactivation can as well be achieved by bystander cell maturation via poly I:C stimulation in vitro and injection of this maturation stimulus in vivo. Preactivation in vivo enhances killing of human leukocyte antigen class I negative tumor cells after their adoptive transfer. These data suggest that a functional, but resting, NK-cell compartment can be established in immune-compromised mice after human hematopoietic progenitor cell transfer.

scholarly journals HTLV-1 propels thymic human T cell development in “human immune system” Rag2-/- IL-2R γc-/- Mice

Retrovirology ◽  
2011 ◽  
Vol 8 (Suppl 1) ◽  
pp. A10 ◽  
Author(s):  
Julien Villaudy ◽  
Melanie Wencker ◽  
Nicolas Gadot ◽  
Jean-Yves Scoazec ◽  
Louis Gazzolo ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Human Immune System ◽  
Human T Cell ◽  
Human Immune

scholarly journals IL-7 Enhances Thymic Human T Cell Development in “Human Immune System” Rag2−/−IL-2Rγc−/−Mice without Affecting Peripheral T Cell Homeostasis

2009 ◽  
Vol 183 (12) ◽  
pp. 7645-7655 ◽  
Author(s):  
Anja U. van Lent ◽  
Wendy Dontje ◽  
Maho Nagasawa ◽  
Rachida Siamari ◽  
Arjen Q. Bakker ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
T Cell Homeostasis ◽  
Human Immune System ◽  
Cell Homeostasis ◽  
Human T Cell ◽  
Human Immune

scholarly journals HTLV-1 Propels Thymic Human T Cell Development in “Human Immune System” Rag2-/- gamma c-/- Mice

2011 ◽  
Vol 7 (9) ◽  
pp. e1002231 ◽  
Author(s):  
Julien Villaudy ◽  
Mélanie Wencker ◽  
Nicolas Gadot ◽  
Nicolas A. Gillet ◽  
Jean-Yves Scoazec ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Development ◽  
Cell Development ◽  
Human Immune System ◽  
Human T Cell ◽  
Human Immune

721 AT1412, a patient-derived CD9 antibody in preclinical development promoting tumor immune infiltration and inducing tumor rejection

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A763-A763
Author(s):  
Remko Schotte ◽  
Julien Villaudy ◽  
Martijn Kedde ◽  
Wouter Pos ◽  
Daniel Go ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Tumor Cells ◽  
Tumor Rejection ◽  
Human Immune System ◽  
Preclinical Development ◽  
High Affinity ◽  
Human Immune ◽  
A375 Melanoma

BackgroundAdaptive immunity to cancer cells forms a crucial part of cancer immunotherapy. Recently, the importance of tumor B-cell signatures were shown to correlate with melanoma survival. We investigated whether tumor-targeting antibodies could be isolated from a patient that cured (now 13 years tumor-free) metastatic melanoma following adoptive transfer of ex vivo expanded autologous T cells.MethodsPatient‘s peripheral blood B cells were isolated and tested for the presence of tumor-reactive B cells using AIMM’s immmortalisation technology. Antibody AT1412 was identified by virtue of its differential binding to melanoma cells as compared to healthy melanocytes. AT1412 binds the tetraspanin CD9, a broadly expressed protein involved in multiple cellular activities in cancer and induces ADCC and ADCP by effector cells.ResultsSpontaneous immune rejection of tumors was observed in human immune system (HIS) mouse models implanted with CD9 genetically-disrupted A375 melanoma (A375-CD9KO) tumor cells, while A375wt cells were not cleared. Most notably, no tumor rejection of A375-CD9KO tumors was observed in NSG mice, indicating that blockade of CD9 makes tumor cells susceptible to immune rejection.CD9 has been described to regulate integrin signaling, e.g. LFA-1, VLA-4, VCAM-1 and ICAM-1. AT1412 was shown to modulate CD9 function by enhancing adhesion and transmigration of T cells to endothelial (HUVEC) cells. AT1412 was most potently enhancing transendothelial T-cell migration, in contrast to a high affinity version of AT1412 or other high affinity anti-CD9 reference antibodies (e.g. ALB6). Enhanced immune cell infiltration is also observed in immunodeficient mice harbouring a human immune system (HIS). AT1412 strongly enhanced CD8 T-cell and macrophage infiltration resulting in tumor rejection (A375 melanoma). PD-1 checkpoint blockade is further sustaining this effect. In a second melanoma model carrying a PD-1 resistant and highly aggressive tumor (SK-MEL5) AT1412 together with nivolumab was inducing full tumor rejection, while either one of the antibodies alone did not.ConclusionsThe safety of AT1412 has been assessed in preclinical development and is well tolerated up to 10 mg/kg (highest dose tested) by non human primates. AT1412 demonstrated a half-life of 8.5 days, supporting 2–3 weekly administration in humans. Besides transient thrombocytopenia no other pathological deviations were observed. No effect on coagulation parameters, bruising or bleeding were observed macro- or microscopically. The thrombocytopenia is reversible, and its recovery accelerated in those animals developing anti-drug antibodies. First in Human clinical study is planned to start early 2021.Ethics ApprovalStudy protocols were approved by the Medical Ethical Committee of the Leiden University Medical Center (Leiden, Netherlands).ConsentBlood was obtained after written informed consent by the patient.

scholarly journals Transplacental priming of the human immune system with environmental allergens can occur early in gestation

2000 ◽  
Vol 106 (3) ◽  
pp. 530-536 ◽  
Author(s):  
Zsolt Szépfalusi ◽  
Josefa Pichler ◽  
Stefan Elsässer ◽  
Katalin van Duren ◽  
Christof Ebner ◽  
...  
Keyword(s):  
Immune System ◽  
Human Immune System ◽  
Human Immune

scholarly journals Antimicrobial peptides: The ancient arm of the human immune system

Virulence ◽  
2010 ◽  
Vol 1 (5) ◽  
pp. 440-464 ◽  
Author(s):  
Jochen Wiesner ◽  
Andreas Vilcinskas
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Human Immune System ◽  
Human Immune

On the use of multiple heterogeneous devices to speedup the execution of a computational model of the Human Immune System

2015 ◽  
Vol 267 ◽  
pp. 304-313 ◽  
Author(s):  
T.M. do Nascimento ◽  
J.M. de Oliveira ◽  
M.P. Xavier ◽  
A.B. Pigozzo ◽  
R.W. dos Santos ◽  
...  
Keyword(s):  
Immune System ◽  
Computational Model ◽  
Human Immune System ◽  
Heterogeneous Devices ◽  
Human Immune
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