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CD34(+) hematopoietic stem cells exert accessory function in lipopolysaccharide-induced T cell stimulation and CD80 expression on monocytes.

Mattern T, Girroleit G, Flad HD, Rietschel ET, Ulmer AJ - J. Exp. Med. (1999)

Bottom Line: CD34(+) hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon gamma production and proliferation.These conclusions are based on the observation that depletion of CD34(+) blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes.The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Cell Biology, Research Center Borstel, 23845 Borstel, Germany. ajulmer@fz-borstel.de

ABSTRACT
CD34(+) hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon gamma production and proliferation. In contrast, stimulation of T cells by "conventional" recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34(+) blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes. The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS. Blood stem cells could be replaced by the hematopoietic stem cell line KG-1a. These findings may be of relevance for high risk patients treated with stem cells or stem cell recruiting compounds and for patients suffering from endotoxin-mediated diseases.

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Related in: MedlinePlus

Accessory cell activity of CD34+ blood stem cells during induction of IFN-γ release in T lymphocytes by LPS. PBMCs (106/ml),  CD34-depleted PBMCs (106/ml), or CD34-depleted PBMCs plus 5%  CD34+ cells were cultured in 24-well plates (1 ml/well) in RPMI 1640  plus 10% HS. Cells were stimulated with LPS (1 μg/ml; black bars); control cultures remained unstimulated (white bars). After 24, 48, or 96 h of  culture, supernatants were harvested and IFN-γ production was measured  in an ELISA. Data are expressed as mean ± SD of duplicate cultures.
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Figure 1: Accessory cell activity of CD34+ blood stem cells during induction of IFN-γ release in T lymphocytes by LPS. PBMCs (106/ml), CD34-depleted PBMCs (106/ml), or CD34-depleted PBMCs plus 5% CD34+ cells were cultured in 24-well plates (1 ml/well) in RPMI 1640 plus 10% HS. Cells were stimulated with LPS (1 μg/ml; black bars); control cultures remained unstimulated (white bars). After 24, 48, or 96 h of culture, supernatants were harvested and IFN-γ production was measured in an ELISA. Data are expressed as mean ± SD of duplicate cultures.

Mentions: In previous experiments, we have shown that LPS is a potent inducer of IFN-γ production by human T lymphocytes (13). In the experiments presented here, we investigated whether depletion of CD34+ blood stem cells also influences the production of IFN-γ by PBMCs. As shown in Fig. 1, IFN-γ production was clearly reduced in the absence of CD34+ cells over the total culture period of 4 d. On the other hand, IFN-γ production could be fully restored by adding CD34+ cells. It should be noted that IFN-γ could be detected in PBMCs or CD34− PBMCs plus CD34+ cells already after 1–2 h of culture (data not given).


CD34(+) hematopoietic stem cells exert accessory function in lipopolysaccharide-induced T cell stimulation and CD80 expression on monocytes.

Mattern T, Girroleit G, Flad HD, Rietschel ET, Ulmer AJ - J. Exp. Med. (1999)

Accessory cell activity of CD34+ blood stem cells during induction of IFN-γ release in T lymphocytes by LPS. PBMCs (106/ml),  CD34-depleted PBMCs (106/ml), or CD34-depleted PBMCs plus 5%  CD34+ cells were cultured in 24-well plates (1 ml/well) in RPMI 1640  plus 10% HS. Cells were stimulated with LPS (1 μg/ml; black bars); control cultures remained unstimulated (white bars). After 24, 48, or 96 h of  culture, supernatants were harvested and IFN-γ production was measured  in an ELISA. Data are expressed as mean ± SD of duplicate cultures.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192932&req=5

Figure 1: Accessory cell activity of CD34+ blood stem cells during induction of IFN-γ release in T lymphocytes by LPS. PBMCs (106/ml), CD34-depleted PBMCs (106/ml), or CD34-depleted PBMCs plus 5% CD34+ cells were cultured in 24-well plates (1 ml/well) in RPMI 1640 plus 10% HS. Cells were stimulated with LPS (1 μg/ml; black bars); control cultures remained unstimulated (white bars). After 24, 48, or 96 h of culture, supernatants were harvested and IFN-γ production was measured in an ELISA. Data are expressed as mean ± SD of duplicate cultures.
Mentions: In previous experiments, we have shown that LPS is a potent inducer of IFN-γ production by human T lymphocytes (13). In the experiments presented here, we investigated whether depletion of CD34+ blood stem cells also influences the production of IFN-γ by PBMCs. As shown in Fig. 1, IFN-γ production was clearly reduced in the absence of CD34+ cells over the total culture period of 4 d. On the other hand, IFN-γ production could be fully restored by adding CD34+ cells. It should be noted that IFN-γ could be detected in PBMCs or CD34− PBMCs plus CD34+ cells already after 1–2 h of culture (data not given).

Bottom Line: CD34(+) hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon gamma production and proliferation.These conclusions are based on the observation that depletion of CD34(+) blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes.The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Cell Biology, Research Center Borstel, 23845 Borstel, Germany. ajulmer@fz-borstel.de

ABSTRACT
CD34(+) hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon gamma production and proliferation. In contrast, stimulation of T cells by "conventional" recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34(+) blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes. The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS. Blood stem cells could be replaced by the hematopoietic stem cell line KG-1a. These findings may be of relevance for high risk patients treated with stem cells or stem cell recruiting compounds and for patients suffering from endotoxin-mediated diseases.

Show MeSH
Related in: MedlinePlus