Flow cytometric analysis of the graft‐versus‐Leukemia‐Effect After Hematopoietic Stem Cell Transplantation in Mice

Abstract

Acute Graft-versus-Host-Disease (aGvHD) is one of the major complications following allogeneic hematopoietic stem cell transplantation (HSCT). Although rather helpful, the use of conventional immunosuppressive drugs leads to general immunosuppression and is toxic. The effects of CD41 T-cells, in respect to the development of aGvHD, can be altered by administration of antihuman CD4 monoclonal antibodies, here MAX.16H5 IgG 1 . This approach must be tested for possible interference with the Graft-versus-Leukemia-Effect (GvL). Thus, in vitro experiments were conducted, exposing P815 leukemic cells to bone marrow and splenocytes from cd4

Incubation of Immune Cell Grafts With MAX.16H5 IgG1 Anti-Human CD4 Antibody Prolonged Survival After Hematopoietic Stem Cell Transplantation in a Mouse Model for Fms Like Tyrosine Kinase 3 Positive Acute Myeloid Leukemia

“…In previous work, our data showed that the short-term ex vivo incubation of an allogeneic graft with the non-depleting anti-human CD4 antibody MAX.16H5 IgG 1 (murine) led to a significant GVHD reduction without negatively influencing the induced GVL effect ( 26 ). Additionally, NOD.Cg-Prkdc scid IL-2rg tm1Wjl /SzJ (NSG) recipient mice showed a significantly increased survival after xenogeneic transplantation of human peripheral blood mononuclear cells when the graft was pre-treated with the anti-human CD4 antibody MAX.16H5 IgG 1 ex vivo ( 27 ).…”

“…Bone marrow cells (BMCs) and splenocytes (SpC) were dissected from CD4/DR3 mice as previously described ( 26 ). BMCs and splenocytes were either incubated with 800 μg MAX.16H5 IgG 1 (1mg/mL, Biotest) per 1.4 × 10 8 cells or without antibody.…”

“…The cell pellets were resuspended in 100 μL 1 × PBS and analyzed by flow cytometry. All samples were measured and analyzed using FACS Canto BD TM II and BD FACSDIVA TM Software (BD Biosciences, Heidelberg, Germany) as previously described ( 26 ).…”

“…In previous studies, we provided evidence that the GVHD development was significantly downregulated by using the MAX.16H5 IgG 1 antibody ( 27 , 29 ). The anti-tumor effect of MAX.16H5 IgG 1 incubated grafts was shown to be concurrently unaffected in a murine mastocytoma model (BALB/c) ( 26 ).…”

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“…Graft‐versus‐host‐disease (GvHD) is a feared, often lethal complication following hematopoietic stem cell transplantation. Schmidt et al demonstrated last year in a mouse model that GvHD of transplanted murine T‐helper cells can be prevented by administration of anti‐human CD4 monoclonal antibodies . As mice can lie, the authors (Hilger et al, this issue, page 803) expanded their experiments by transplanting human leukocytes into another mouse model.…”