scid Mice as Recipients of an Adoptive Immune Response

1992 ◽  
pp. 303-304
Author(s):  
H. C. Schuppe ◽  
M. Lamers ◽  
J. Langhorne ◽  
H. Mossmann
Keyword(s):  
Immune Response ◽  
Scid Mice

Human Immune Response to a Peptide Mimic ofNeisseria meningitidisSerogroup C in hu-PBMC-SCID Mice

Hybridoma ◽  
1999 ◽  
Vol 18 (2) ◽  
pp. 121-129 ◽  
Author(s):  
WENDY A. HUTCHINS ◽  
THOMAS KIEBER-EMMONS ◽  
GEORGE M. CARLONE ◽  
M.A. JULIE WESTERINK
Keyword(s):  
Immune Response ◽  
Scid Mice ◽  
Peptide Mimic ◽  
Human Immune Response ◽  
Human Immune

scholarly journals Coxiella burnetii Interaction with Neutrophils and MacrophagesIn Vitroand in SCID Mice following Aerosol Infection

2013 ◽  
Vol 81 (12) ◽  
pp. 4604-4614 ◽  
Author(s):  
Alexandra Elliott ◽  
Ying Peng ◽  
Guoquan Zhang
Keyword(s):  
Immune Response ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Natural Infection ◽  
Scid Mice ◽  
Innate Immune ◽  
Content Type ◽  
Aerosol Infection

ABSTRACTCoxiella burnetiiis an obligate intracellular bacterium that causes acute and chronic Q fever in humans. Human Q fever is mainly transmitted by aerosol infection. However, there is a fundamental gap in the knowledge regarding the mechanisms of pulmonary immunity againstC. burnetiiinfection. This study focused on understanding the interaction betweenC. burnetiiand innate immune cellsin vitroandin vivo. Both virulentC. burnetiiNine Mile phase I (NMI) and avirulent Nine Mile phase II (NMII) were able to infect neutrophils, while the infection rates were lower than 29%, suggesting thatC. burnetiican infect neutrophils, but infection is limited. Interestingly,C. burnetiiinside neutrophils can infect and replicate within macrophages, suggesting that neutrophils cannot killC. burnetiiandC. burnetiimay be using infection of neutrophils as an evasive strategy to infect macrophages. To elucidate the mechanisms of the innate immune response toC. burnetiinatural infection, SCID mice were exposed to aerosolizedC. burnetii. Surprisingly, neutrophil influx into the lungs was delayed until day 7 postinfection in both NMI- and NMII-infected mice. This result suggests that neutrophils may play a unique role in the early immune response against aerosolizedC. burnetii. Studying the interaction betweenC. burnetiiand the innate immune system can provide a model system for understanding how the bacteria evade early immune responses to cause infection.

scholarly journals Duodenal Helminth Infection Alters Barrier Function of the Colonic Epithelium via Adaptive Immune Activation

2011 ◽  
Vol 79 (6) ◽  
pp. 2285-2294 ◽  
Author(s):  
Chien-wen Su ◽  
Yue Cao ◽  
Jess Kaplan ◽  
Mei Zhang ◽  
Wanglin Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Barrier Function ◽  
Helminth Infection ◽  
Scid Mice ◽  
Ultrastructural Changes ◽  
Intestinal Helminth ◽  
Epithelial Barrier ◽  
Epithelial Permeability ◽  
Content Type ◽  
The Impact

ABSTRACTChronic infection with intestinal helminth parasites is a major public health problem, particularly in the developing world, and can have significant effects on host physiology and the immune response to other enteric infections and antigens. The mechanisms underlying these effects are not well understood. In the current study, we investigated the impact of infection with the murine nematode parasiteHeligmosomoides polygyrus, which resides in the duodenum, on epithelial barrier function in the colon. We found thatH. polygyrusinfection produced a significant increase in colonic epithelial permeability, as evidenced by detection of elevated serum levels of the tracer horseradish peroxidase following rectal administration. This loss of normal barrier function was associated with clear ultrastructural changes in the tight junctions of colonic epithelial cells and an alteration in the expression and distribution of the junctional protein E-cadherin. These parasite-induced abnormalities were not observed in SCID mice but did occur in SCID mice that were adoptively transferred with wild-type T cells, indicating a requirement for adaptive immunity. Furthermore, the helminth-induced increase in gut permeability was not seen in STAT6 knockout (KO) mice. Taken together, the results demonstrate that one of the mechanisms by which helminths exert their effects involves the lymphocyte- and STAT6-dependent breakdown of the intestinal epithelial barrier. This increase in epithelial permeability may facilitate the movement of lumenal contents across the mucosa, thus helping to explain how helminth infection can alter the immune response to enteric antigens.

scholarly journals Efficacy of Ravuconazole in Treatment of Mucosal Candidosis in SCID Mice

2001 ◽  
Vol 45 (12) ◽  
pp. 3433-3436 ◽  
Author(s):  
Karl V. Clemons ◽  
David A. Stevens
Keyword(s):  
Immune Response ◽  
Body Weight ◽  
Small Intestine ◽  
Candida Albicans ◽  
Dimethyl Sulfoxide ◽  
Carboxymethyl Cellulose ◽  
Oral Treatment ◽  
Scid Mice ◽  
Aids Patients ◽  
Once Daily

ABSTRACT A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment. Mice were infected orally withCandida albicans and received either no treatment or oral treatment once daily for 12 days with 1, 5, or 25 mg of ravuconazole per kg of body weight per day, 5 or 25 mg of fluconazole per kg per day, or diluent (10% dimethyl sulfoxide in 0.5% carboxymethyl cellulose). The numbers of C. albicans CFU in the esophagus, stomach, small intestine, and cecum on day 25 in mice given no treatment and diluent were equivalent. Both doses of fluconazole significantly reduced numbers of CFU in all four tissues but were equivalent to each other. Ravuconazole showed dose-responsive improvement of clearance of CFU. Ravuconazole at 25 mg/kg was superior in reduction of numbers of CFU in all tissues to controls or 25 mg of fluconazole per kg and to other regimens in at least three tissues. Fluconazole at 25 mg/kg cured no infection in any tissue, whereas 25 mg of ravuconazole/kg cleared infection in all tissues from 50% of mice. Ravuconazole has good efficacy and the potential to cure mucosal candidosis in the absence of a functional immune response.

scholarly journals Helicobacter pylori with a Truncated Lipopolysaccharide O Chain Fails To Induce Gastritis in SCID Mice Injected with Splenocytes from Wild-Type C57BL/6J Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 3925-3931 ◽  
Author(s):  
K. A. Eaton ◽  
S. M. Logan ◽  
P. E. Baker ◽  
R. A. Peterson ◽  
M. A. Monteiro ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Immune Responses ◽  
Scid Mice ◽  
Delayed Type Hypersensitivity ◽  
Wild Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Ifn Γ ◽  
H Pylori

ABSTRACT The goal of this study was to determine whether Helicobacter pylori lipopolysaccharide (LPS) O-chain polysaccharide contributes to gastritis in a mouse model. C57BL/6J or C57BL/6-Prkdcscid (severe combined immunodeficient [SCID]) mice were inoculated with H. pylori strain SS1 or SS1::0826kan, in which a β-1,4-galactosyltransferase (HP0826), an LPS biosynthetic enzyme, had been disrupted. H. pylori strain SS1::0826kan expresses truncated LPS lacking O chain. Recipient SCID mice were given C57BL/6J splenocytes by intraperitoneal injection. Bacterial colonization, gastric lesions (gastritis, neutrophilic infiltration, and gastric epithelial metaplasia), cellular (delayed-type hypersensitivity) and humoral immune responses to H. pylori sonicate, and gastric gamma interferon (IFN-γ) mRNA expression were quantified. Recipient SCID mice colonized by H. pylori strain SS1 developed extensive gastritis with loss of normal fundic gland morphology. In contrast, gastric mucosa of recipient SCID mice colonized by H. pylori strain SS1::0826kan was not statistically distinguishable from that of uninfected recipient mice. Delayed-type hypersensitivity and humoral immune responses were detected in infected mice inoculated with wild-type SS1, but not with SS1::0826kan. IFN-γ transcription was lower in mice infected with SS1::0826kan than in mice infected with SS1. In this model of rapidly progressive gastritis due to H. pylori, the O chain contributed to the extent of gastritis and to the host immune response. These data support a role for H. pylori LPS O chain in direct induction of the host immune response leading to gastritis and gastric damage and are in contrast to protein antigens, such as urease and cag products which do not contribute to gastritis in mice.

Human UCB CD133+ Cell Infusion In NOD-SCID Mice with Acute Hind Limb Ischemia Improves Reperfusion of An Ischemic Bed

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4697-4697
Author(s):  
Mathew Lesniewski ◽  
Jonathan Goldberg ◽  
Laura Fanning-Hammond ◽  
Marcie Finney ◽  
Margaret Forster ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Array ◽  
Limb Ischemia ◽  
Surface Antigens ◽  
Scid Mice ◽  
Th2 Response ◽  
Inflammatory Gene ◽  
Anti Inflammatory

Abstract Abstract 4697 Clinical trials have shown intracoronary or intramuscular injections of hematopoietic stem cells (HSC) ameliorate vascular ischemia. HSCs are isolated from bone marrow (BM), umbilical cord blood (UCB), and adult peripheral blood (AB). Critical limb ischemia patients, injected with autologous HSC into ischemic tissue had improved perfusion and reduced amputations. However, autologous HSC effectiveness declines with age. We hypothesized that UCB CD133+ HSCs’ are more efficacious than autologous HSC at revascularization for an ischemic bed. Immune reactive surface antigens on UCB CD133+ cells were determined using multi-parameter flow cytometry. UCB CD133+ allogeneic immune responses from 72 h co-cultures were analyzed using a mixed lymphocyte culture (MLR) proliferation assays, and induced cytokine production found using TH1(inflammatory)/TH2(anti-inflammatory) cytometric bead assays (CBA) (BD Biosciences (San Jose, CA). In vivo studies were done using NOD/SCID mice treated with low-dose irradiation (200cGy) then femoral ligation. Study mice were divided into 3 treatment groups and underwent intracoronary infusions of; 1×106 UCB CD133+, 0.5×106 UCB mononuclear cells (MNCs), or EGM media alone. Day 3 post-ligation and cell infusion, quadriceps from 3 mice in each group were harvested, total RNA isolated using Trizol™ and RNA for each treatment group pooled. Pooled RNA was converted to cDNA then assayed using mouse ABI Affymetrix™ Gene chip. Computational pathway analyzes were run for significant transcriptome changes. Gene array data was confirmed on select genes using quantitative reverse transcriptase real time PCR (qPCR). Treated mice were followed for ischemic bed reperfusion by Laser Doppler imaging for 28 days post-ligation. UCB CD133+ cells express MHC class I and II, but lack CD80 and CD86. Allogeneic MLR assays using UCB and AB MNCs showed UCB CD133+ cells were stimulatory to MNC proliferation. The MNCs alloresponse to UCB CD133+ cells produced high concentration of interleukin 4 (IL-4) and IL-10 indicative of a TH2 response. These results show allogeneic UCB CD133+ cells induce a TH2 immune response due to an absence of co-stimulation of immune cells. To verify whether the results are recapitulated in vivo, we treated acute limb ischemia in NOD/SCID mice with human UCB CD133+ cells and monitored revascularization by blood flow and Affymetrix mouse gene array. Computational analysis of Affymetrix mouse gene arrays from comparing all 3 treatment protocols indicated that ischemic quadriceps treated with UCB CD133+ cells exhibited a significant enrichment of anti-angiogeneic, chemotaxic, cytokine, and immune response genes. UCB CD133+ treated mice had increase expression of anti-inflammatory, and anti-angiogeneic genes versus controls. Conversely media and UCB MNC treated mice had equal to or higher pro-inflammatory gene expression. The anti-inflammatory gene response was confirmed for 2 of the 3 genes, arginase 1, CXCL7, and tumor growth factor beta binding protein 2 (TGFβBP2) comparing CD133+ treated mice to UCB MNC treated mice. TGFβBP2 was not observed to change in vivo. UCB CD133+ cells treated mice also had improved blood perfusion of the ischemic bed at 28 days post-ligation versus control protocols. The in vivo mouse model supports the in vitro observation, but demonstrates improved reperfusion over controls. Currently there are 2 non-exclusive hypotheses for the function of CD133+ cells in revascularization. First the CD133+ cells integrate and differentiate into new vascular endothelial cells and the second is that the CD133+ cells augment revascularization via a paracrine effect which does not require integration into the host tissue. In vitro studies suggest that UCB CD133+ cells promote an allogeneic TH2 type response because of a lack of co-stimulatory immune surface antigens, resulting in high concentrations of IL-4 and IL-10. This skewed TH2 response inhibits inflammation, the subsequent tissue damage, and may augment revascularization. Although these studies cannot exclude a role for UCB CD133+ cellular integration, results support the paracrine hypothesis as infusion of selected CD133+ cells appears to promote an anti-inflammatory, anti-angiogenic profile at day 3 post-ligation and at 1 month improved reperfusion compared with non-selected MNC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic Control of Experimental Lyme Arthritis in the Absence of Specific Immunity

1999 ◽  
Vol 67 (4) ◽  
pp. 1967-1973 ◽  
Author(s):  
Charles R. Brown ◽  
Steven L. Reiner
Keyword(s):  
Immune Response ◽  
Gene Knockout ◽  
Scid Mice ◽  
Lyme Arthritis ◽  
Mouse Strains ◽  
Specific Immunity ◽  
Severe Arthritis ◽  
Severity Scores ◽  
C3h Mice ◽  
Rag 1

ABSTRACT Host genetics play an important role in determining resistance or susceptibility to experimental Lyme arthritis. While specific immunity appears to regulate disease resolution, innate immunity appears to regulate disease severity. Intradermal infection with Borrelia burgdorferi yields severe arthritis in C3H/He (C3H) mice but only minimal arthritis in BALB/c mice. Intradermal infection of immunodeficient C3H SCID mice also results in severe arthritis, but arthritis of only moderate severity in BALB/c SCID mice. In the present study, we examined immunodeficient recombinase-activating gene-knockout (RAG-1 −/−) (RAG−) mice from resistant C57BL/6 (B6) and DBA/2 (DBA) mouse strains. B. burgdorferi-infected B6 RAG− and DBA RAG− mice had little or no ankle swelling, a low occurrence of inflammatory infiltrates in tibiotarsal joints, and low arthritis severity scores in comparison to RAG+ and RAG− BALB/c or C3H mice. Few differences in spirochete DNA levels in ankles of resistant and susceptible RAG− mice were seen. These data suggest that resistance to arthritis development following B. burgdorferi infection is not necessarily dependent on an acquired immune response and can occur despite the presence of high spirochete burden. Thus, genes expressed outside the specific immune response can be central regulators of experimental arthritis.

scholarly journals Potent Immune Response against HIV-1 and Protection from Virus Challenge in hu-PBL-SCID Mice Immunized with Inactivated Virus-pulsed Dendritic Cells Generated in the Presence of IFN-α

2003 ◽  
Vol 198 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Caterina Lapenta ◽  
Stefano M. Santini ◽  
Mariantonia Logozzi ◽  
Massimo Spada ◽  
Mauro Andreotti ◽  
...  
Keyword(s):  
Immune Response ◽  
Therapeutic Vaccine ◽  
Vaccination Schedule ◽  
T Cell Response ◽  
Scid Mice ◽  
Virus Challenge ◽  
Gm Csf ◽  
Human Immune Response ◽  
Anti Hiv ◽  
Hiv 1

A major challenge of AIDS research is the development of therapeutic vaccine strategies capable of inducing the humoral and cellular arms of the immune responses against HIV-1. In this work, we evaluated the capability of DCs pulsed with aldrithiol-2–inactivated HIV-1 in inducing a protective antiviral human immune response in SCID mice reconstituted with human PBL (hu-PBL-SCID mice). Immunization of hu-PBL-SCID mice with DCs generated after exposure of monocytes to GM-CSF/IFN-α (IFN-DCs) and pulsed with inactivated HIV-1 resulted in a marked induction of human anti–HIV-1 antibodies, which was associated with the detection of anti-HIV neutralizing activity in the serum. This vaccination schedule also promoted the generation of a human CD8+ T cell response against HIV-1, as measured by IFN-γ Elispot analysis. Notably, when the hu-PBL-SCID mice immunized with antigen-pulsed IFN-DCs were infected with HIV-1, inhibition of virus infection was observed as compared with control animals. These results suggest that IFN-DCs pulsed with inactivated HIV-1 can represent a valuable approach of immune intervention in HIV-1–infected patients.

scholarly journals Type I Interferon as a Powerful Adjuvant for Monocyte-Derived Dendritic Cell Development and Activity in Vitro and in Hu-Pbl-Scid Mice

2000 ◽  
Vol 191 (10) ◽  
pp. 1777-1788 ◽  
Author(s):  
Stefano M. Santini ◽  
Caterina Lapenta ◽  
Mariantonia Logozzi ◽  
Stefania Parlato ◽  
Massimo Spada ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cell ◽  
Scid Mice ◽  
Primary Immune Response ◽  
Type I ◽  
Antitumor Effects ◽  
Gm Csf ◽  
Type I Ifns ◽  
Hiv 1

Type I interferons (IFNs) are cytokines exhibiting antiviral and antitumor effects, including multiple activities on immune cells. However, the importance of these cytokines in the early events leading to the generation of an immune response is still unclear. Here, we have investigated the effects of type I IFNs on freshly isolated granulocyte/macrophage colony-stimulating factor (GM-CSF)–treated human monocytes in terms of dendritic cell (DC) differentiation and activity in vitro and in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) mice. Type I IFNs induced a surprisingly rapid maturation of monocytes into short-lived tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)–expressing DCs endowed with potent functional activities, superior with respect to the interleukin (IL)-4/GM-CSF treatment, as shown by FACS® analyses, mixed leukocyte reaction assays with allogeneic PBLs, and lymphocyte proliferation responses to HIV-1–pulsed autologous DCs. Type I IFN induced IL-15 production and strongly promoted a T helper cell type 1 response. Notably, injection of IFN-treated HIV-1–pulsed DCs in SCID mice reconstituted with autologous PBLs resulted in the generation of a potent primary immune response, as evaluated by the detection of human antibodies to various HIV-1 antigens. These results provide a rationale for using type I IFNs as vaccine adjuvants and support the concept that a natural alliance between these cytokines and monocytes/DCs represents an important early mechanism for connecting innate and adaptive immunity.

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