NDLI: Differential immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO) on primary human CD4$^{+}$ and CD8$^{+}$ T cells

Content Provider	Springer Nature Link
Author	Forouzandeh, Farshad Jalili, Reza B. Germain, Marc Duronio, Vincent Ghahary, Aziz
Copyright Year	2007
Abstract	We have previously demonstrated that indoleamine 2,3-dioxygenase (IDO) expression by skin cells generates a tryptophan deficient environment in which THP-1, Jurkat cells as well as human PBMC are unable to survive. However, the subsets of primary human T cells that are sensitive to tryptophan depletion have not been identified. In this study, we asked whether the proliferation and viability of bystander CD4$^{+}$ and CD8$^{+}$ T cells are modulated in response to IDO induced tryptophan deficient environment and if so, whether their response is different. To address these questions, we co-cultured IDO-expressing fibroblasts with bystander human CD4$^{+}$ and CD8$^{+}$ T cells for 4 days and then the survival and proliferation rates as well as downstream metabolic pathway of tryptophan degradation in these cells were evaluated. The results showed a marked immunosuppressive effect of IDO expression on both subsets of primary human T cells. Interestingly, there was also a significant difference in the suppressive effect of IDO on proliferation of CD8$^{+}$ compared to that of CD4$^{+}$ T cells. The results of subsequent experiments showed that this discrepancy is due to differences in GCN2 kinase pathway activation between these two sets of immune cells. In conclusion, the finding of this study revealed that the proliferation of CD8$^{+}$ and CD4$^{+}$ T cells are suppressed in response to tryptophan deficient environment caused by IDO expression and it is more so for CD8$^{+ }$T than CD4$^{+ }$T cells.
Starting Page	1
Ending Page	7
Page Count	7
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	309
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2007-11-16
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Indoleamine 2,3-dioxygenase (IDO) GCN2 kinase pathway Kynurenine Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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