Induction of a secondary human HPA-5B alloimmune response in SCID mice engrafted with human lymphocytes and antigen-pulsed autologous dendritic cells

Severe combined immunodeficient (SCID) mice are increasingly used as hosts for the adoptive transfer of human lymphocytes. Human antibody responses can be obtained in these xenogeneic chimeras, but information about the functionality of the human T cells in SCID mice is limited and controversial. Studies using human peripheral blood lymphocytes (PBL) injected intraperitoneally (IP) into SCID mice (hu-PBL-SCID mice) have shown that human T cells from these chimeras are anergic and have a defective signaling via the T-cell receptor. In addition, their antigenic repertoire is limited to xenoreactive clones. In the present study, we tested the functionality of human T cell in a recently described chimeric model. In this system, BALB/c mice are conditioned by irradiation and then transplanted with SCID bone marrow, followed by IP injection of human PBL. Our experiments demonstrated that human T cells, recovered from these hu-PBL-BALB mice within 1 month posttransplant, proliferated and expressed activation markers upon stimulation with anti-CD3 monoclonal antibody. A vigorous antiallogeneic human cytotoxic T-lymphocyte (CTL) response could be generated in these mice by immunizing them with irradiated allogeneic cells. Moreover, anti-human immunodeficiency virus type 1 (HIV-1) Net- specific human CTLs could be generated in vivo from naive lymphocytes by immunization of mouse-human chimeras with a recombinant vaccinia-nef virus. This model may be used to evaluate potential immunomodulatory drugs or cytokines, and could provide a relevant model for testing HIV vaccines, for production of antiviral T-cell clones for adoptive therapy, and for studying human T-cell responses in vivo.

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Effects of subtoxic concentrations of TiO2 and ZnO nanoparticles on human lymphocytes, dendritic cells and exosome production

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2012.07.021 ◽

2012 ◽

Vol 264 (1) ◽

pp. 94-103 ◽

Cited By ~ 57

Author(s):

Britta Andersson-Willman ◽

Ulf Gehrmann ◽

Zekiye Cansu ◽

Tina Buerki-Thurnherr ◽

Harald F. Krug ◽

...

Keyword(s):

Dendritic Cells ◽

Zno Nanoparticles ◽

Human Lymphocytes

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Generation of biliary lesions after transfer of human lymphocytes into severe combined immunodeficient (SCID) mice.

Journal of Experimental Medicine ◽

10.1084/jem.170.6.1919 ◽

1989 ◽

Vol 170 (6) ◽

pp. 1919-1930 ◽

Cited By ~ 120

Author(s):

S M Krams ◽

K Dorshkind ◽

M E Gershwin

Keyword(s):

Bile Duct ◽

Human Lymphocytes ◽

Severe Combined Immunodeficiency ◽

Serum Levels ◽

Scid Mice ◽

Lymphoid Cells ◽

Biliary Cirrhosis ◽

Human Mononuclear Cell ◽

Mononuclear Infiltrate ◽

Immunodeficiency Disease

Human PBL have been reported to reconstitute B and T cells as well as human serum Ig in mice with severe combined immunodeficiency disease (SCID). To confirm these observations and attempt the transfer of an autoimmune disease to the immunodeficient animals, groups of SCID mice received an injection of PBL from patients with primary biliary cirrhosis (PBC) or from normal volunteers. By 8 wk after the injection of 10-42 x 10(6) PBL into the mice, human lymphoid cells were detected in the spleen of approximately half of the animals and all had detectable serum levels of human IgG. Moreover, the sera of SCID mice that received cells from patients with PBC contained human antimitochondrial antibodies (AMA) to dihydrolipoamide acetyltransferase, the major mitochondrial autoantigen of PBC. Histologically, a human mononuclear cell infiltrate was present around the portal areas of the liver and inflammation, bile duct atypica, and necrosis of bile duct cells were observed. While the biliary lesions in the SCID recipients of PBC cells were more severe, a mononuclear infiltrate was clearly evident in mice that received cells from normal donors, suggesting the presence of a graft-vs.-host-like disease. While these data are the first to describe an animal model with both the humoral and cellular characteristics of PBC, they also raise an interesting question regarding the preferential localization of lymphoid cells to the biliary system.

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Periodontal immune responses of human lymphocytes in Actinobacillus actinomycetemcomitans-inoculated NOD/SCID mice engrafted with peripheral blood leukocytes of periodontitis patients

Journal of Periodontal Research ◽

10.1111/j.1600-0765.1999.tb02222.x ◽

1999 ◽

Vol 34 (1) ◽

pp. 54-61 ◽

Cited By ~ 21

Author(s):

Y.-T. A. Teng ◽

H. Nguyen ◽

A. Hassanloo ◽

R. P. Ellen ◽

N. Hozumi ◽

...

Keyword(s):

Immune Responses ◽

Peripheral Blood ◽

Human Lymphocytes ◽

Scid Mice ◽

Actinobacillus Actinomycetemcomitans ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes

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Gamma-globulin modulates growth of EBV-derived B-cell tumors in scid mice reconstituted with human lymphocytes

International Journal of Cancer ◽

10.1002/ijc.2910550522 ◽

1993 ◽

Vol 55 (5) ◽

pp. 824-829 ◽

Cited By ~ 6

Author(s):

Mohammad R. Abedi ◽

Birger Christensson ◽

Salahuddin Al-Masud ◽

Lennart Hammarström ◽

C. I. Smith

Keyword(s):

B Cell ◽

Gamma Globulin ◽

Human Lymphocytes ◽

Scid Mice

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MEK inhibition, alone or in combination with BRAF inhibition, impairs multiple functions of isolated normal human lymphocytes and dendritic cells

Journal for ImmunoTherapy of Cancer ◽

10.1186/2051-1426-1-s1-p93 ◽

2013 ◽

Vol 1 (S1) ◽

Cited By ~ 2

Author(s):

Laura J Vella ◽

Anupama Pasam ◽

Nektaria Dimopoulos ◽

Miles Andrews ◽

Anne-Laure Puaux ◽

...

Keyword(s):

Dendritic Cells ◽

Human Lymphocytes ◽

Multiple Functions ◽

Mek Inhibition ◽

Braf Inhibition ◽

Normal Human

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Using the NOD/SCID Mice Model of Human Erythroleukemia for Evaluating the Cytotoxicity Activity of CB-CIK/NK Cells Stimulated by K562-DCs Fusion Vaccines.

Blood ◽

10.1182/blood.v106.11.5240.5240 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5240-5240

Author(s):

Yang Li ◽

Shaoliang Huang ◽

Jianpei Fang ◽

Xuchao Zhang ◽

Jing Wei ◽

...

Keyword(s):

Dendritic Cells ◽

Nk Cells ◽

K562 Cells ◽

Scid Mice ◽

Tumour Mass ◽

Mice Model ◽

Cytotoxicity Activity ◽

Group A ◽

Group D

Abstract CD3+CD56+ cytokine-induced killer (CIK) cells are prospective effectors for adoptive immunotherapy, CIK/NK cells incubated with K562-dendritic cells (DCs) fusion vaccines have more higher cytotoxicity activity. In this study, the efficacy and the safety of application of cord blood (CB) derived CIK/NK cells stimulated by K562-dendritic cells (DCs) fusion vaccines were evaluated in vivo by the NOD/SCID mice model of human erythroleukemia (K562 line, CD13+). DCs and CIK/NK cells were inducted by combination of cytokines from CB MNCs, DCs were fused with inactivated K562 tumor line by PEG (mw1500). 5 days before the harvest of CIK/NK cells, 1×105 K562-DCs fusion vaccines were co-cultured with 1×106 CB-CIK/NK cells to prepare for the K562-DCs fusion vaccines stimulated CIK/NK cells. NOD/SCID mice divided into six groups, eight in one group. Mice in A,B and C groups were inoculated with 1×106 K562 cells by tail vein. 24 hours later, 1×107 K562-DCs fusion vaccines stimulated CIK/NK cells and 1×107 unstimulated CIK/NK cells were transfued into the mice of group A and B, respectively. Group D and E were K562-DCs fusion vaccines stimulated CIK/NK cells and no-stimulated CIK/NK cells control, transfued by 1×107 stimulated CIK/NK cells and 1×107 no-stimulated CIK/NK cells, respectively. Group F is a normal control that no any inoculation were taken. None of the NOD/SCID mice in group C that inoculated with 1×106 K562 cells survived longer than 39 days, hepatosplenomegalic mass was seen in five mice. Death in group A and B were only one and two, respectively, at day 65 and day 56, 62. There was no tumour mass can be seen in group A and B, and the survial were more than 70 days. Both survival time of group A(69.38±1.77 days) and B(67.25±5.34 days) were longer than that of group C(30.38±4.57 days) significantly (P<0.01). The tumor marker (CD13) in periperal blood, live and lung of CIK/NK cells treated NOD/SCID mice (group A and B) significantly less than group C(P<0.01). There was no difference of CD56 positive in periperal blood of group A and B survival mice between that of the control (group D and E). These result indicated that K562-DCs fusion vaccines stimulating CB-CIK/NK cells have a potent anti-tumour activity in vivo and without any side-effect.

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