Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism

Content Provider	Scilit
Author	Liu, Zhiwei Dai, Hehua Wan, Ni Wang, Tao Bertera, Suzanne Trucco, Massimo
Copyright Year	2007
Description	Dendritic cell-derived indoleamine 2,3-dioxygenase (IDO) suppresses naive T cell proliferation and induces their apoptosis by catalyzing tryptophan, and hence is essential for the maintenance of peripheral tolerance. However, it is not known whether memory T cells are subject to the regulation by IDO-mediated tryptophan catabolism, as memory T cells respond more rapidly and vigorously than their naive counterparts and are resistant to conventional costimulatory blockade. In this study, we present the evidence that memory $CD8^{+}$ T cells are susceptible to tryptophan catabolism mediated by IDO. We found that overexpression of IDO in vivo attenuated the generation of both central memory $CD8^{+}$ T cells $(T_{CM}$) and effector memory $CD8^{+}$ T cells $(T_{EM}$) while suppressing IDO activity promoted their generation. Moreover, IDO overexpression suppressed the effector function of $T_{CM}$ cells or $T_{CM}$ cell-mediated allograft rejection as well as their proliferation in vivo. Interestingly, $T_{CM}$ cells were resistant to apoptosis induced by tryptophan catabolism. However, IDO overexpression did not suppress the effector function of $T_{EM}$ cells or $T_{EM}$ cell-mediated allograft rejection, suggesting that $T_{EM}$ cells, unlike $T_{CM}$ cells, do not require tryptophan for their effector function once they are generated. This study provides insight into the mechanisms underlying the differential regulation of memory T cell responsiveness and has clinical implications for vaccination or tolerance induction.
Ending Page	4266
Page Count	7
Starting Page	4260
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.178.7.4260
Journal	The Journal of Immunology
Issue Number	7
Volume Number	178
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2007-04-01
Access Restriction	Open
Subject Keyword	Tryptophan Catabolism
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology