Blockade of Cd40-Cd154 Interferes with Human T cell Engraftment in Scid Mice

Foy, Teresa M.; McIlraith, M.; Masters, Sally R.; Dunn, Jonathan J.; Rossini, Aldo A.; Shultz, Leonard D.; Hesselton, Ruth; Wagar, Eric J.; Lipsky, Peter E.; Noelle, Randolph J.; Greiner, Dale L.

doi:10.1177/096368979800700105

Cited by 8 publications

(1 citation statement)

References 31 publications

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“…As shown previously (33), human CD4 ϩ and CD8 ϩ cell engraftment was also inhibited by treatment with anti-human CD154 mAb, a costimulation molecule expressed predominately on activated CD4 ϩ , but not CD8 ϩ , T cells (Table IV).…”

Section: Cd4 ϩ Cells and Cd40-cd154 Interactions Are Required For Engsupporting

confidence: 77%

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: Cd4 ϩ Cells and Cd40-cd154 Interactions Are Required For Engsupporting

confidence: 77%

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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Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?

Aloui

Sut

Prigent

et al. 2014

Sci Rep

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The CD40 ligand (CD40L/CD154), a member of TNF superfamily, is notably expressed on activated CD4+ T-cells and stimulated platelets. CD40L is linked to a variety of pathologies and to acute transfusion reactions (ATR). Mutations in this gene (CD40LG) lead to X-linked hyper-IgM syndrome. Some CD40LG polymorphisms are associated with variable protein expression. The rationale behind this study is that CD40L protein has been observed to be involved in ATR. We wondered whether genetic polymorphisms are implicated. We investigated genetic diversity in the CD40LG using DHPLC and capillary electrophoresis for screening and genotyping (n = 485 French and Tunisian blood donors). We identified significant difference in the CD40LG linkage pattern between the two populations. Variant minor alleles were significantly over-represented in Tunisian donors (P<0.0001 to 0.0270). We found higher heterogeneity in the Tunisian, including three novel low frequency variants. As there was not a particular pattern of CD40LG in single apheresis donors whose platelet components induced an ATR, we discuss how this information may be useful for future disease association studies on CD40LG.

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Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model1

Kanmaz

Fechner²,

Torrealba³

et al. 2004

Transplantation

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Blockade of Cd40-Cd154 Interferes with Human T cell Engraftment in Scid Mice

Cited by 8 publications

References 31 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

Are polymorphisms of the immunoregulatory factor CD40LG implicated in acute transfusion reactions?

Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model1

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