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CD11b super(+)/Gr-1 super(+) Myeloid Suppressor Cells Cause T Cell Dysfunction after Traumatic Stress
T cell dysfunction that occurs after surgery or trauma is associated with a poor clinical outcome. We describe that myeloid suppressor cells expressing CD11b super(+)/Gr-1 super(+) markers invade the spleen after traumatic stress and suppress T cell function through the production of arginase 1. We...
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Published in: | Journal of Immunology 2006-02, Vol.176 (4), p.2085-2094 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | T cell dysfunction that occurs after surgery or trauma is associated with a poor clinical outcome. We describe that myeloid suppressor cells expressing CD11b super(+)/Gr-1 super(+) markers invade the spleen after traumatic stress and suppress T cell function through the production of arginase 1. We created a consistent model of traumatic stress in C57BL/6 mice to perform this work. A significant number of CD11b super(+)/Gr-1 super(+) cells expressing arginase 1 accumulated in T cell zones around the germinal centers of the white pulp of the spleen within 6 h of trauma and lasted for at least 72 h. Increased arginase activity and arginase 1 expression, along with increased [ super(3)H]arginine uptake, L-arginine depletion, and L-ornithine accumulation in the culture medium, were observed exclusively in CD11b super(+)/Gr-1 super(+) cells after traumatic stress. Flow cytometry revealed CD11b super(+)/Gr-1 super(+) as a heterogeneous myeloid suppressor cell also expressing low levels of MHC class I and II, CD80, CD86, CD31, and others. When compared with controls, trauma-induced CD11b super(+)/Gr-1 super(+) cells significantly inhibited CD3/CD28-mediated T cell proliferation, TCR zeta -chain expression, and IL-2 production. The suppressive effects by trauma CD11b super(+)/Gr-1 super(+) cells were overcome with the arginase antagonist N-hydroxy-nor-L-arginine or extrasupplementation of medium with L-arginine. Poor Ag-presenting capacity of control and trauma-induced CD11b super(+)/Gr-1 super(+) cells was detected in allogeneic murine leukocyte reaction. This study demonstrates that CD11b super(+)/Gr-1 super(+) cells invade the spleen following traumatic stress and cause T cell dysfunction by an arginase-mediated mechanism, probably that of arginine depletion. Understanding the mechanism of immune suppression by these cells has important clinical implications in the treatment of immune dysfunction after trauma or surgery. |
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ISSN: | 0022-1767 1365-2567 |