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CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress
Valeriya P Makarenkova1, Vishal Bansal, Benjamin M Matta
1Department of Surgery, University of Pittsburgh Medical Center, PA 15213, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|February 4, 2006
Summary
Traumatic stress causes myeloid suppressor cells (CD11b+/Gr-1+) to invade the spleen, suppressing T cell function via arginase 1. This immune suppression mechanism, linked to poor outcomes, can be reversed by blocking arginase or supplementing L-arginine.
Area of Science:
- Immunology
- Cell Biology
- Stress Physiology
Background:
- T cell dysfunction post-surgery or trauma correlates with adverse clinical outcomes.
- Myeloid suppressor cells (MSCs) play a critical role in immune regulation.
Purpose of the Study:
- To investigate the role of myeloid suppressor cells in T cell dysfunction following traumatic stress.
- To elucidate the mechanism by which MSCs suppress T cell function after trauma.
Main Methods:
- A mouse model of traumatic stress was established in C57BL/6 mice.
- Flow cytometry and cell-based assays were used to analyze splenic immune cell populations and function.
- Arginase activity, L-arginine levels, and T cell proliferation/cytokine production were measured.
Main Results:
- Traumatic stress led to the accumulation of CD11b+/Gr-1+ myeloid suppressor cells in the spleen.
- These cells expressed arginase 1, depleted L-arginine, and suppressed T cell proliferation, TCR zeta-chain expression, and IL-2 production.
- Arginase inhibition or L-arginine supplementation reversed the suppressive effects.
Conclusions:
- CD11b+/Gr-1+ myeloid suppressor cells infiltrate the spleen after trauma and induce T cell dysfunction through an arginase-mediated mechanism, likely L-arginine depletion.
- Understanding this mechanism offers potential therapeutic targets for post-trauma immune dysfunction.