Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hainz, U; Obexer, P; Winkler, C; Sedlmayr, P; Takikawa, O; Greinix, H; Lawitschka, A; Pötschger, U; Fuchs, D; Ladisch, S; Heitger, A.
Monocyte-mediated T-cell suppression and augmented monocyte tryptophan catabolism after human hematopoietic stem-cell transplantation.
BLOOD. 2005; 105(10): 4127-4134.
Doi: 10.1182/blood-2004-05-1726
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- Co-Autor*innen der Med Uni Graz
- Greinix Hildegard
- Sedlmayr Peter
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- Abstract:
- T-cell dysfunction after human hematopoietic stem-cell transplantation (HSCT) is generally attributed to intrinsic T-cell defects. Here we show that the characteristic impaired proliferative responses to polyclonal stimulation of post-HSCT peripheral blood mononuclear cells (PB-MCs) were markedly (4-fold) improved by T-cell enrichment. Conversely, addback of post-HSCT monocytes to these enriched T cells dampened their proliferative responses, suggesting that post-HSCT monocytes effectively mediate T-cell suppression. As a mechanism possibly contributing to monocyte-mediated T-cell suppression, we investigated monocyte tryptophan catabolism by indoleamine 2,3-dioxygenase into kynurenine, which has been implicated in regulating T-cell responses. Compared with controls, all post-HSCT monocyte-containing cell cultures (total PBMCs, monocytes, and monocyte/T-cell cocultures), but not monocyte-depleted populations, secreted elevated amounts of kynurenine. Blockade of tryptophan catabolism improved the proliferative responses. The slightly increased kynurenine release and substantial release of neopterin by unstimulated post-HSCT monocytes suggests that they were in a state of continuous activation. Superimposed on this state, stimulation of these cells caused a striking, additional increase (10-fold) in kynurenine release, and they triggered marked apoptosis of autologous post-HSCT T cells. We conclude that the amplified kynurenine release by post-HSCT monocytes, particularly induced upon stimulation, may underlie their suppressor activity, which in turn may contribute to the depressed T-cell immune responses after HSCT.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Apoptosis -
- Cell Proliferation -
- Cells, Cultured -
- Child -
- Child, Preschool -
- Female -
- Hematopoietic Stem Cell Transplantation -
- Humans -
- Kynurenine - metabolism Kynurenine - secretion
- Male -
- Middle Aged -
- Monocytes - metabolism Monocytes - physiology Monocytes - secretion
- T-Lymphocytes - cytology T-Lymphocytes - metabolism
- Tryptophan - metabolism
- Tryptophan Oxygenase - antagonists & inhibitors Tryptophan Oxygenase - metabolism