T cell stimulus-induced crosstalk between lymphocytes and liver macrophages results in augmented cytokine release.
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T cell stimulus-induced crosstalk between lymphocytes and liver macrophages results in augmented cytokine release. / Gantner, F; Leist, M; Küsters, S; Vogt, K; Volk, H D; Tiegs, Gisa.
In: EXP CELL RES, Vol. 229, No. 1, 1, 1996, p. 137-146.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - T cell stimulus-induced crosstalk between lymphocytes and liver macrophages results in augmented cytokine release.
AU - Gantner, F
AU - Leist, M
AU - Küsters, S
AU - Vogt, K
AU - Volk, H D
AU - Tiegs, Gisa
PY - 1996
Y1 - 1996
N2 - Polyclonal T cell stimulation in humans leads to a cytokine burst syndrome that may result in organ failure or lethality. Mechanisms of such cytokine-dependent morbidity can be studied in mice challenged with the T cell mitogen concanavalin A (Con A). In this model tumor necrosis factor (TNF)-dependent toxicity is characterized by a relatively selective liver failure. We examined here whether a crosstalk between liver macrophages and lymphocytes may be the underlying cause for the overshooting TNF response. Lymphocytes from lymph nodes, thymus, or the spleen were cocultured with Kupffer cells and stimulated with the polyclonal T cell stimuli Con A, anti-CD3 mAb, or staphylococcal enterotoxin B. We observed a rapid and synergistically augmented release of TNF, and also of IL-1, IL-2, IL-4, IL-6, and IFN-gamma, compared to stimulation of the individual cell types alone. This dramatically upregulated cytokine response did not require direct cell contact, but was mediated by a soluble factor. In order to find out whether TNF upregulation would require additional cell types in the liver, we used cocultures of T cells and a macrophage cell line and confirmed our previous results. In this model system an increase in TNF mRNA was observed in macrophages, but not in T cells. We conclude that the T cell-macrophage crosstalk following polyclonal T cell stimulation may be responsible for an overshooting TNF release from macrophages. This mechanism finally may lead to organ damage such as liver injury upon Con A injection into mice.
AB - Polyclonal T cell stimulation in humans leads to a cytokine burst syndrome that may result in organ failure or lethality. Mechanisms of such cytokine-dependent morbidity can be studied in mice challenged with the T cell mitogen concanavalin A (Con A). In this model tumor necrosis factor (TNF)-dependent toxicity is characterized by a relatively selective liver failure. We examined here whether a crosstalk between liver macrophages and lymphocytes may be the underlying cause for the overshooting TNF response. Lymphocytes from lymph nodes, thymus, or the spleen were cocultured with Kupffer cells and stimulated with the polyclonal T cell stimuli Con A, anti-CD3 mAb, or staphylococcal enterotoxin B. We observed a rapid and synergistically augmented release of TNF, and also of IL-1, IL-2, IL-4, IL-6, and IFN-gamma, compared to stimulation of the individual cell types alone. This dramatically upregulated cytokine response did not require direct cell contact, but was mediated by a soluble factor. In order to find out whether TNF upregulation would require additional cell types in the liver, we used cocultures of T cells and a macrophage cell line and confirmed our previous results. In this model system an increase in TNF mRNA was observed in macrophages, but not in T cells. We conclude that the T cell-macrophage crosstalk following polyclonal T cell stimulation may be responsible for an overshooting TNF release from macrophages. This mechanism finally may lead to organ damage such as liver injury upon Con A injection into mice.
KW - Animals
KW - Male
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred BALB C
KW - Kinetics
KW - Cell Line
KW - Polymerase Chain Reaction
KW - Macrophages/immunology
KW - Interferon-gamma/biosynthesis
KW - Concanavalin A/pharmacology
KW - Interleukin-6/biosynthesis
KW - Tumor Necrosis Factor-alpha/biosynthesis
KW - Cytokines/biosynthesis
KW - Interleukin-4/biosynthesis
KW - T-Lymphocytes/immunology
KW - Cell Communication/drug effects/immunology
KW - Kupffer Cells/immunology
KW - Liver/immunology
KW - Lymph Nodes/immunology
KW - Spleen/immunology
KW - Thymus Gland/immunology
KW - Animals
KW - Male
KW - Cells, Cultured
KW - Mice
KW - Mice, Inbred BALB C
KW - Kinetics
KW - Cell Line
KW - Polymerase Chain Reaction
KW - Macrophages/immunology
KW - Interferon-gamma/biosynthesis
KW - Concanavalin A/pharmacology
KW - Interleukin-6/biosynthesis
KW - Tumor Necrosis Factor-alpha/biosynthesis
KW - Cytokines/biosynthesis
KW - Interleukin-4/biosynthesis
KW - T-Lymphocytes/immunology
KW - Cell Communication/drug effects/immunology
KW - Kupffer Cells/immunology
KW - Liver/immunology
KW - Lymph Nodes/immunology
KW - Spleen/immunology
KW - Thymus Gland/immunology
M3 - SCORING: Journal article
VL - 229
SP - 137
EP - 146
JO - EXP CELL RES
JF - EXP CELL RES
SN - 0014-4827
IS - 1
M1 - 1
ER -
