| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Surgery and
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213
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 
-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.
This article has been cited by other articles:
|
|
 |
|
  D. Ilkovitch and D. M. Lopez The Liver Is a Site for Tumor-Induced Myeloid-Derived Suppressor Cell Accumulation and Immunosuppression Cancer Res., July 1, 2009; 69(13): 5514 - 5521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Stewart, D. J. Liewehr, S. M. Steinberg, K. M. Greeneltch, and S. I. Abrams Modulating the Expression of IFN Regulatory Factor 8 Alters the Protumorigenic Behavior of CD11b+Gr-1+ Myeloid Cells J. Immunol., July 1, 2009; 183(1): 117 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Liu, C. Zhang, A. Sun, Y. Zheng, L. Wang, and X. Cao Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I J. Immunol., May 15, 2009; 182(10): 6207 - 6216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ilkovitch and D. M. Lopez Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec Blood, May 7, 2009; 113(19): 4729 - 4739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ostrand-Rosenberg and P. Sinha Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer J. Immunol., April 15, 2009; 182(8): 4499 - 4506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Morris, S. M. Heidorn, D. R. Herbert, C. Perkins, D. A. Hildeman, M. V. Khodoun, and F. D. Finkelman Endogenously Produced IL-4 Nonredundantly Stimulates CD8+ T Cell Proliferation J. Immunol., February 1, 2009; 182(3): 1429 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Flohe, S. Flohe, and F. U. Schade Invited review: Deterioration of the immune system after trauma: signals and cellular mechanisms Innate Immunity, December 1, 2008; 14(6): 333 - 344. [Abstract] [PDF]
|
|
|
|
 |
|
 P. A. Nigrovic, D. H.D. Gray, T. Jones, J. Hallgren, F. C. Kuo, B. Chaletzky, M. Gurish, D. Mathis, C. Benoist, and D. M. Lee Genetic Inversion in Mast Cell-Deficient Wsh Mice Interrupts Corin and Manifests as Hematopoietic and Cardiac Aberrancy Am. J. Pathol., December 1, 2008; 173(6): 1693 - 1701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Winfield, M. J. Delano, K. Pande, P. O. Scumpia, D. LaFace, and L. L. Moldawer Myeloid-Derived Suppressor Cells in Cancer Cachexia Syndrome: A New Explanation for an Old Problem JPEN J Parenter Enteral Nutr, November 1, 2008; 32(6): 651 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Heithoff, E. Y. Enioutina, D. Bareyan, R. A. Daynes, and M. J. Mahan Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity Infect. Immun., November 1, 2008; 76(11): 5191 - 5199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-I. Youn, S. Nagaraj, M. Collazo, and D. I. Gabrilovich Subsets of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice J. Immunol., October 15, 2008; 181(8): 5791 - 5802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bryk, J. B. Ochoa, M. I. T. Correia, V. Munera-Seeley, and P. J. Popovic Effect of Citrulline and Glutamine on Nitric Oxide Production in RAW 264.7 Cells in an Arginine-Depleted Environment JPEN J Parenter Enteral Nutr, July 1, 2008; 32(4): 377 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kobayashi, T. Yoshida, D. Takeuchi, V. C. Jones, K. Shigematsu, D. N. Herndon, and F. Suzuki Gr-1+CD11b+ cells as an accelerator of sepsis stemming from Pseudomonas aeruginosa wound infection in thermally injured mice J. Leukoc. Biol., June 1, 2008; 83(6): 1354 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tschop, A. Martignoni, H. S. Goetzman, L. G. Choi, Q. Wang, J. G. Noel, C. K. Ogle, T. A. Pritts, J. A. Johannigman, A. B. Lentsch, et al. {gamma}{delta} T cells mitigate the organ injury and mortality of sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 581 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Vaknin, L. Blinder, L. Wang, R. Gazit, E. Shapira, O. Genina, M. Pines, E. Pikarsky, and M. Baniyash A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression Blood, February 1, 2008; 111(3): 1437 - 1447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Scumpia, M. J. Delano, K. M. Kelly-Scumpia, J. S. Weinstein, J. L. Wynn, R. D. Winfield, C. Xia, C. S. Chung, A. Ayala, M. A. Atkinson, et al. Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis Blood, November 15, 2007; 110(10): 3673 - 3681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Marhaba, M. Vitacolonna, D. Hildebrand, M. Baniyash, P. Freyschmidt-Paul, and M. Zoller The Importance of Myeloid-Derived Suppressor Cells in the Regulation of Autoimmune Effector Cells by a Chronic Contact Eczema J. Immunol., October 15, 2007; 179(8): 5071 - 5081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zhu, Y. Bando, S. Xiao, K. Yang, A. C. Anderson, V. K. Kuchroo, and S. J. Khoury CD11b+Ly-6Chi Suppressive Monocytes in Experimental Autoimmune Encephalomyelitis J. Immunol., October 15, 2007; 179(8): 5228 - 5237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Delano, P. O. Scumpia, J. S. Weinstein, D. Coco, S. Nagaraj, K. M. Kelly-Scumpia, K. A. O'Malley, J. L. Wynn, S. Antonenko, S. Z. Al-Quran, et al. MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis J. Exp. Med., June 11, 2007; 204(6): 1463 - 1474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yu, C. Liu, K. Su, J. Wang, Y. Liu, L. Zhang, C. Li, Y. Cong, R. Kimberly, W. E. Grizzle, et al. Tumor Exosomes Inhibit Differentiation of Bone Marrow Dendritic Cells J. Immunol., June 1, 2007; 178(11): 6867 - 6875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Popovic, H. J. Zeh III, and J. B. Ochoa Arginine and Immunity J. Nutr., June 1, 2007; 137(6): 1681S - 1686S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, S. Yu, J. Kappes, J. Wang, W. E. Grizzle, K. R. Zinn, and H.-G. Zhang Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host Blood, May 15, 2007; 109(10): 4336 - 4342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kim, P. P. Sarangi, Y. Lee, S. Deshpande Kaistha, S. Lee, and B. T. Rouse Depletion of MCP-1 increases development of herpetic stromal keratitis by innate immune modulation J. Leukoc. Biol., December 1, 2006; 80(6): 1405 - 1415. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
