CD11b+/Gr-1+ Myeloid Suppressor Cells Cause T Cell Dysfunction after Traumatic Stress
| Autor: | Juan B. Ochoa, Vishal Bansal, Valeriya P. Makarenkova, Lori Perez, Benjamin M. Matta |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Myeloid T-Lymphocytes T cell Immunology Receptors Antigen T-Cell Biology Arginine Mice Immune system Antigen Stress Physiological medicine Animals Immunology and Allergy Cell Lineage Myeloid Cells Cells Cultured Cell Proliferation CD86 CD11b Antigen Membrane Proteins Germinal center Immunohistochemistry Molecular biology Mice Inbred C57BL Arginase Phenotype medicine.anatomical_structure Interleukin-2 Wounds and Injuries Receptors Chemokine Spleen CD80 |
| Zdroj: | The Journal of Immunology. 176:2085-2094 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.176.4.2085 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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