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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
CD28 ligation increases macrophage suppression of T-cell proliferation
Daniel Silberman1, Amanda Bucknum, Thomas Bartlett
1Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
Abstract:
When compared to spleen or lymph node cells, resident peritoneal cavity cells respond poorly to T-cell activation in vitro. The greater proportional representation of macrophages in this cell source has been shown to actively suppress the T-cell response. Peritoneal macrophages exhibit an immature phenotype (MHC class II(lo), B7(lo)) that reduces their efficacy as antigen-presenting cells. Furthermore, these cells readily express inducible nitric oxide synthase (iNOS), an enzyme that promotes T-cell tolerance by catabolism of the limiting amino acid arginine. Here, we investigate the ability of exogenous T-cell costimulation to recover the peritoneal T-cell response. We show that CD28 ligation failed to recover the peritoneal T-cell response and actually suppressed responses that had been recovered by inhibiting iNOS. As indicated by cytokine ELISpot and neutralizing monoclonal antibody (mAb) treatment, this 'cosuppression' response was due to CD28 ligation increasing the number of interferon (IFN)-γ-secreting cells. Our results illustrate that cellular composition and cytokine milieu influence T-cell costimulation biology.Cellular & Molecular Immunology advance online publication, 23 April 2012; doi:10.1038/cmi.2012.13.
Insights
Resident peritoneal cells poorly activate T-cells due to macrophages. Suppressing inducible nitric oxide synthase (iNOS) partially restored T-cell responses, but CD28 ligation further suppressed them by increasing interferon-gamma production.
Area of Science:
- Immunology
- Cell Biology
Background:
- Resident peritoneal cavity cells exhibit poor T-cell activation compared to spleen or lymph node cells.
- Peritoneal macrophages, prevalent in this cell population, suppress T-cell responses due to an immature phenotype and inducible nitric oxide synthase (iNOS) expression, which catabolizes arginine and promotes T-cell tolerance.
Purpose of the Study:
- To investigate the efficacy of exogenous T-cell costimulation in restoring the peritoneal T-cell response.
- To understand the mechanisms underlying the interaction between T-cell costimulation and peritoneal macrophage-mediated suppression.
Main Methods:
- In vitro T-cell activation assays using peritoneal cells.
- Inhibition of inducible nitric oxide synthase (iNOS).
- CD28 ligation for T-cell costimulation.
- Cytokine ELISpot assays and neutralizing monoclonal antibody (mAb) treatment to assess T-cell responses and cytokine production.
Main Results:
- CD28 ligation failed to recover the peritoneal T-cell response.
- CD28 ligation suppressed T-cell responses previously recovered by iNOS inhibition.
- This suppression, termed 'cosuppression,' was attributed to CD28 ligation increasing the number of interferon-gamma (IFN-γ)-secreting cells.
Conclusions:
- Cellular composition and the cytokine milieu significantly influence T-cell costimulation biology.
- Exogenous T-cell costimulation via CD28 ligation can have suppressive effects in the peritoneal environment.
- Understanding these complex interactions is crucial for modulating immune responses in vivo.
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