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Immune responses by cord blood cells.

Roncarolo Mg, Mike Bigler, E Ciuti, Sabata Martino, Pier‐Angelo Tovo

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Abstract

In the present study, the biological properties of cord blood cells were investigated. Cord blood mononuclear cells and T cells responded normally to activation by alloantigens in primary mixed leukocyte reactions (MLRs), indicating that cord blood T cells can be normally activated via their TcR and have normal proliferative capacities. In addition, they expressed normal levels of accessory molecules such as CD28 and LFA-1, which contribute to amplify their responses. In contrast, cord blood mononuclear cells, but not cord blood monocytes, had a reduced capacity to stimulate allogeneic cells in primary MLRs. In addition, cord blood monocytes express lower levels of HLA-DR and ICAM-1 compared to adult peripheral blood monocytes. Cord blood mononuclear cells were also impaired in their capacity to generate allogeneic cytotoxic activity in primary mixed leukocyte cultures (MLCs). In contrast, cord blood B cells were similar to adult B cells in their capacity to switch to immunoglobulin E producing cells when incubated with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody. We also demonstrated that IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) production by activated cord blood mononuclear cells was comparable to that observed with peripheral blood mononuclear cells isolated from normal adult donors. In contrast, interferon-gamma (IFN-gamma) was significantly decreased, whereas IL-4 and IL-5 were absent. Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were in general higher in the supernatants of cord blood cells. Thus, cord blood immune responses differ from those of peripheral blood at several levels. Whether these differences account for a reduced capacity of transplanted cord blood cells to modulate graft vs. host disease remains to be determined.

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What this paper is about

In the present study, the biological properties of cord blood cells were investigated. Cord blood mononuclear cells and T cells responded normally to activation by alloantigens in primary mixed leukocyte reactions (MLRs), indicating that cord blood T cells can be normally activated via their TcR and have normal proliferative capacities. In addition, they expressed normal levels of accessory molecules such as CD28 and LFA-1, which contribute to amplify their responses. In contrast, cord blood mononuclear cells, but not cord blood monocytes, had a reduced capacity to stimulate allogeneic cells in primary MLRs. In addition, cord blood monocytes express lower levels of HLA-DR and ICAM-1 compared to adult peripheral blood monocytes. Cord blood mononuclear cells were also impaired in their capacity to generate allogeneic cytotoxic activity in primary mixed leukocyte cultures (MLCs). In contrast, cord blood B cells were similar to adult B cells in their capacity to switch to immunoglobulin E producing cells when incubated with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody. We also demonstrated that IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) production by activated cord blood mononuclear cells was comparable to that observed with peripheral blood mononuclear cells isolated from normal adult donors. In contrast, interferon-gamma (IFN-gamma) was significantly decreased, whereas IL-4 and IL-5 were absent. Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were in general higher in the supernatants of cord blood cells. Thus, cord blood immune responses differ from those of peripheral blood at several levels. Whether these differences account for a reduced capacity of transplanted cord blood cells to modulate graft vs. host disease remains to be determined.

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Available abstract

In the present study, the biological properties of cord blood cells were investigated. Cord blood mononuclear cells and T cells responded normally to activation by alloantigens in primary mixed leukocyte reactions (MLRs), indicating that cord blood T cells can be normally activated via their TcR and have normal proliferative capacities. In addition, they expressed normal levels of accessory molecules such as CD28 and LFA-1, which contribute to amplify their responses. In contrast, cord blood mononuclear cells, but not cord blood monocytes, had a reduced capacity to stimulate allogeneic cells in primary MLRs. In addition, cord blood monocytes express lower levels of HLA-DR and ICAM-1 compared to adult peripheral blood monocytes. Cord blood mononuclear cells were also impaired in their capacity to generate allogeneic cytotoxic activity in primary mixed leukocyte cultures (MLCs). In contrast, cord blood B cells were similar to adult B cells in their capacity to switch to immunoglobulin E producing cells when incubated with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody. We also demonstrated that IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) production by activated cord blood mononuclear cells was comparable to that observed with peripheral blood mononuclear cells isolated from normal adult donors. In contrast, interferon-gamma (IFN-gamma) was significantly decreased, whereas IL-4 and IL-5 were absent. Granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were in general higher in the supernatants of cord blood cells. Thus, cord blood immune responses differ from those of peripheral blood at several levels. Whether these differences account for a reduced capacity of transplanted cord blood cells to modulate graft vs. host disease remains to be determined.

Key concepts: Cord blood, Peripheral blood mononuclear cell, Immune system, Immunology, Monocyte, Tumor necrosis factor alpha, Medicine, Biology

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