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CD28 ligation increases macrophage suppression of T-cell proliferation

Cellular & Molecular Immunology volume 9, pages 341–349 (2012)Cite this article

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 IIlo, B7lo) 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.

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Acknowledgements

This work was supported by grants (R15 AI 060356-01, R15 CA 136901-01) to J Riggs from the NIH AREA program. D Silberman was supported by fellowships from the New Jersey Commission for Cancer Research and the Rider University Marvin Talmadge Memorial Research Fund. A Walker was supported by a Rider University Undergraduate Research Scholar Award and was the recipient of a Van Arman Scholarship Award from the Inflammation Research Association. We are grateful to A Sepulveda, S Wisniewski, S Homan and D Marshall for mouse husbandry.

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Authors and Affiliations

  1. Department of Biology, Rider University, Lawrenceville, 08648, NJ, USA

    Daniel Silberman, Amanda Bucknum, Thomas Bartlett, Gabriella Composto, Megan Kozlowski, Amanda Walker, Amy Werda, Jackelyn Cua & James E Riggs

  2. Department of Pathology, Harvard Medical School, Cambridge, 02115, MA, USA

    Arlene H Sharpe

  3. Immunosciences, Bristol-Myers Squibb, Princeton, 08543, NJ, USA

    John E Somerville

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Correspondence to James E Riggs.

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Silberman, D., Bucknum, A., Bartlett, T. et al. CD28 ligation increases macrophage suppression of T-cell proliferation. Cell Mol Immunol 9, 341–349 (2012). https://doi.org/10.1038/cmi.2012.13

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