Abstract
Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.
| Original language | English |
|---|---|
| Pages (from-to) | 301-305 |
| Number of pages | 5 |
| Journal | Trends in Immunology |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
L-arginine metabolism in myeloid cells controls T-lymphocyte functions. / Bronte, Vincenzo; Serafini, Paolo; Mazzoni, Alessandra; Segal, David M.; Zanovello, Paola.
In: Trends in Immunology, Vol. 24, No. 6, 01.06.2003, p. 301-305.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - L-arginine metabolism in myeloid cells controls T-lymphocyte functions
AU - Bronte, Vincenzo
AU - Serafini, Paolo
AU - Mazzoni, Alessandra
AU - Segal, David M.
AU - Zanovello, Paola
PY - 2003/6/1
Y1 - 2003/6/1
N2 - Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.
AB - Although current attention has focused on regulatory T lymphocytes as suppressors of autoimmune responses, powerful immunosuppression is also mediated by a subset of myeloid cells that enter the lymphoid organs and peripheral tissues during times of immune stress. If these myeloid suppressor cells (MSCs) receive signals from activated T lymphocytes in the lymphoid organs, they block T-cell proliferation. MSCs use two enzymes involved in arginine metabolism to control T-cell responses: inducible nitric oxide synthase (NOS2), which generates nitric oxide (NO) and arginase 1 (Arg1), which depletes the milieu of arginine. Th1 cytokines induce NOS2, whereas Th2 cytokines upregulate Arg1. Induction of either enzyme alone results in a reversible block in T-cell proliferation. When both enzymes are induced together, peroxynitrites, generated by NOS2 under conditions of limiting arginine, cause activated T lymphocytes to undergo apoptosis. Thus, NOS2 and Arg1 might act separately or synergistically in vivo to control specific types of T-cell responses, and selective antagonists of these enzymes might prove beneficial in fighting diseases in which T-cell responses are inappropriately suppressed. This Opinion is the second in a series on the regulation of the immune system by metabolic pathways.
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UR - http://www.scopus.com/inward/citedby.url?scp=0038519365&partnerID=8YFLogxK
U2 - 10.1016/S1471-4906(03)00132-7
DO - 10.1016/S1471-4906(03)00132-7
M3 - Article
C2 - 12810105
AN - SCOPUS:0038519365
VL - 24
SP - 301
EP - 305
JO - Trends in Immunology
JF - Trends in Immunology
SN - 1471-4906
IS - 6
ER -