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CD11b+/Gr-1+ Myeloid Suppressor Cells Cause T Cell Dysfunction after Traumatic Stress
| Content Provider | Scilit |
|---|---|
| Author | Makarenkova, Valeriya P. Bansal, Vishal Matta, Benjamin M. Perez, Lori Ann Ochoa, Juan B. |
| Copyright Year | 2006 |
| Description | T cell dysfunction that occurs after surgery or trauma is associated with a poor clinical outcome. We describe that myeloid suppressor cells expressing CD11b+/Gr-1+ 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+/Gr-1+ 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 [3H]arginine uptake, l-arginine depletion, and l-ornithine accumulation in the culture medium, were observed exclusively in CD11b+/Gr-1+ cells after traumatic stress. Flow cytometry revealed CD11b+/Gr-1+ 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+/Gr-1+ cells significantly inhibited CD3/CD28-mediated T cell proliferation, TCR ζ-chain expression, and IL-2 production. The suppressive effects by trauma CD11b+/Gr-1+ 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+/Gr-1+ cells was detected in allogeneic murine leukocyte reaction. This study demonstrates that CD11b+/Gr-1+ 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. |
| Ending Page | 2094 |
| Page Count | 10 |
| Starting Page | 2085 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.176.4.2085 |
| Journal | The Journal of Immunology |
| Issue Number | 4 |
| Volume Number | 176 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2006-02-15 |
| Access Restriction | Open |
| Subject Keyword | Invade the Spleen Spleen After Traumatic Traumatic Stress |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
