Related Experiment Video
Updated: May 2, 2026
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
CD90(+)CD45(-) intraperitoneal mesothelial-like cells inhibit T cell activation by production of arginase I
Joji Kitayama1, Shigenobu Emoto1, Hironori Yamaguchi1
1Department of Surgical Oncology, University of Tokyo, Tokyo, Japan.
Abstract:
In this study, we analyzed intraperitoneal cells recovered from human samples and found that CD90(+)CD45(-) cells exist as a minor population but vigorously grow in culture, showing the morphological features of mesothelial cells (MC). Interestingly, the MC highly expressed arginase I and markedly suppressed T cell proliferation with the reduction of CD3 ζ chain expression in T cells stimulated by coated anti-CD3 mAb. The addition of nor-NOHA (500 μM), or L-arginine (1 mM) mostly restored the inhibitory effect of MC on T cell proliferation as well as the reduced expression of CD3 ζ chain. The expression level of CD3 ζ chain in T cells in the peritoneal cavity was significantly down-regulated from circulating T cells. These results suggest that intraperitoneal free MC have immunomodulatory functions through the control of L-arginine level, and thus may play significant roles in the pathogenesis of various diseases in the peritoneal cavity.
Insights
Peritoneal mesothelial cells (MC) suppress T cell proliferation by reducing L-arginine levels. Restoring L-arginine levels reversed this immunosuppression, suggesting MC play a role in peritoneal disease pathogenesis.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Intraperitoneal cells include a minor CD90(+)CD45(-) population with mesothelial cell (MC) morphology.
- Mesothelial cells (MC) are known for their role in the peritoneum, but their immunomodulatory functions are not fully understood.
Purpose of the Study:
- To investigate the immunomodulatory functions of intraperitoneal mesothelial cells (MC).
- To explore the mechanism by which MC affect T cell proliferation and function.
Main Methods:
- Analysis of intraperitoneal cells from human samples.
- Cell culture of CD90(+)CD45(-) cells.
- Assessment of T cell proliferation and CD3 ζ chain expression.
- Treatment with arginase I inhibitor (nor-NOHA) and L-arginine.
Main Results:
- CD90(+)CD45(-) cells exhibited MC morphology and suppressed T cell proliferation.
- MC expressed arginase I, leading to reduced CD3 ζ chain expression in T cells.
- Nor-NOHA or L-arginine addition restored T cell proliferation and CD3 ζ chain expression.
- CD3 ζ chain expression was lower in peritoneal T cells compared to circulating T cells.
Conclusions:
- Intraperitoneal MC possess immunomodulatory capabilities via L-arginine metabolism.
- MC-mediated L-arginine depletion contributes to T cell suppression in the peritoneal cavity.
- These findings highlight MC's potential role in peritoneal disease pathogenesis.
