Murine IL-2 receptor beta chain blockade improves human leukocyte engraftment in SCID mice

Tournoy, Kurt G.; Depraetere, Stany; Meuleman, Philip; Leroux‐Roels, Geert; Pauwels, Romain

doi:10.1002/(sici)1521-4141(199810)28:10<3221::aid-immu3221>3.0.co;2-s

Cited by 35 publications

(50 citation statements)

References 37 publications

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“…NOD-scid-B2m null mice support heightened levels of human T cell engraftment, and in contrast to that observed in Hu-PBL-NOD-scid mice, there was a normal ratio of CD4:CD8 human cells in Hu-PBL-NOD-scid-B2m null mice (20). The basis of these differences in human cell engraftment could result from differences in host NK cell activity or from the absence of host MHC class I (20,35,36).…”

Section: Discussionmentioning

confidence: 99%

“…IL-2R ␤-chain (CD122) is expressed on mouse NK cells, granulocytes, and, to a lesser extent, many other cell types (37,38). Administration of TM-␤1 mAb to Hu-PBL-C.B-17-scid mice has been shown to increase human cell engraftment (36). Our present data show that human cell proliferation is increased in NOD-scid mice treated with anti-mouse CD122 mAb, and that this treatment leads to a CD4:CD8 ratio similar to that observed in NOD-scid-B2m null mice.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Human Cell Engraftment and Development of EBV-Related Lymphoproliferative Disorders in Hu-PBL-scidMice

Wagar

Cromwell²,

Shultz

et al. 2000

The Journal of Immunology

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Human PBMC engraft in mice homozygous for the severe combined immunodeficiency (Prkdcscid) mutation (Hu-PBL-scid mice). Hu-PBL-NOD-scid mice generate 5- to 10-fold higher levels of human cells than do Hu-PBL-C.B-17-scid mice, and Hu-PBL-NOD-scid β2-microglobulin-null (NOD-scid-B2mnull) mice support even higher levels of engraftment, particularly CD4+ T cells. The basis for increased engraftment of human PBMC and the functional capabilities of these cells in NOD-scid and NOD-scid-B2mnull mice are unknown. We now report that human cell proliferation in NOD-scid mice increased after in vivo depletion of NK cells. Human cell engraftment depended on CD4+ cells and required CD40-CD154 interaction, but engrafted CD4+ cells rapidly became nonresponsive to anti-CD3 Ab stimulation. Depletion of human CD8+ cells led to increased human CD4+ and CD20+ cell engraftment and increased levels of human Ig. We further document that Hu-PBL-NOD-scid mice are resistant to development of human EBV-related lymphoproliferative disorders. These disorders, however, develop rapidly following depletion of human CD8+ cells and are prevented by re-engraftment of CD8+ T cells. These data demonstrate that 1) murine NK cells regulate human cell engraftment in scid recipients; 2) human CD4+ cells are required for human CD8+ cell engraftment; and 3) once engrafted, human CD8+ cells regulate human CD4+ and CD20+ cell expansion, Ig levels, and outgrowth of EBV-related lymphoproliferative disorders. We propose that the Hu-PBL-NOD-scid model is suitable for the in vivo analysis of immunoregulatory interactions between human CD4+ and CD8+ cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regulation of Human Cell Engraftment and Development of EBV-Related Lymphoproliferative Disorders in Hu-PBL-scidMice

Wagar

Cromwell²,

Shultz

et al. 2000

The Journal of Immunology

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“…1 day before transplantation. TM␤1 is a rat anti-mouse anti-IL-2R ␤-chain mAb that depletes the murine NK cells (19). Human PBMC containing 3 ϫ 10 6 B lymphocytes, or a maximum of 70 ϫ 10 6 human PBMC (depending on the buffy coat), were dissolved in PBS and injected i.p.…”

Section: Transfer Of Pbmc To Scid/scid Mice and Immunization Of Scid/mentioning

confidence: 93%

Human Memory B Lymphocyte Subsets Fulfill Distinct Roles in the Anti-Polysaccharide and Anti-Protein Immune Response

Moens

Wuyts

Meyts

et al. 2008

The Journal of Immunology

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There is controversy on the role of IgM memory and switched memory B lymphocytes in the Ab response to T cell-independent and T cell-dependent Ags. We transplanted SCID/SCID mice with human B lymphocyte subsets and immunized them with heat-inactivated Streptococcus pneumoniae or with a pneumococcal vaccine. Inactivated S. pneumoniae and soluble pneumococcal capsular polysaccharides elicited an IgM anti-polysaccharide and anti-protein Ab response from IgM memory B lymphocytes and an IgG anti-polysaccharide and anti-protein response from switched memory B lymphocytes. In addition to the IgM Ab response, IgM memory B cells elicited an IgG anti-polysaccharide and anti-protein Ab response after immunization with inactivated S. pneumoniae or soluble pneumococcal capsular polysaccharides. In conclusion, our findings provide evidence for a versatile role of IgM memory B cells in T-independent and T-dependent immune responses.

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“…injection. Pretreatment of SCID/SCID mice with TM g 1 significantly improves the survival and functionality of the graft [29]. HMC were dissolved in 500 ?…”

Section: Transferring Hmc To Scid/scid Micementioning

confidence: 99%

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

et al. 2004

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Protection against infections with Streptococcus pneumoniae is mediated by antibodies against the capsular polysaccharides (caps-PS). Here we show that in in vitro experiments CD4 + T lymphocytes stimulate and CD8 + T lymphocytes inhibit the human anti-caps-PS antibody response. Using antagonistic anti-CD40 and antagonistic anti-CD40 ligand (CD40L) monoclonal antibodies, we showed that the CD4 + T lymphocyte-mediated stimulation is dependent on the CD40-CD40L interaction. The role of CD40L was further illustrated by the observation that CD4 + T lymphocytes obtained from a patient with hyper-IgM syndrome were unable to enhance the immune response to caps-PS. Furthermore, CD4 + T lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps-PS, failed to stimulate the antibody response of adult B lymphocytes to caps-PS. These in vitro findings were confirmed by in vivo experiments in which SCID/SCID mice were reconstituted with human mononuclear cells. Furthermore, we showed that caps-PS induce production of IL-4, IL-6, IL-10, and IFN-+ , and that this enhanced production was inhibited by blocking the CD40-CD40L interaction. This is the first demonstration that the human immune response to caps-PS, which is markedly regulated by T lymphocytes, is dependent on the CD40-CD40L interaction.

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Murine IL-2 receptor beta chain blockade improves human leukocyte engraftment in SCID mice

Cited by 35 publications

References 37 publications

Regulation of Human Cell Engraftment and Development of EBV-Related Lymphoproliferative Disorders in Hu-PBL-scidMice

Regulation of Human Cell Engraftment and Development of EBV-Related Lymphoproliferative Disorders in Hu-PBL-scidMice

Human Memory B Lymphocyte Subsets Fulfill Distinct Roles in the Anti-Polysaccharide and Anti-Protein Immune Response

The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40‐CD40 ligand interaction

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