Silberman, DanielBucknum, AmandaBartlett, ThomasComposto, GabriellaKozlowski, MeganWalker, AmandaWerda, AmyCua, JackelynSomerville, John E.Riggs, James E.Sharpe, Arlene2013-05-082012Silberman, Daniel, Amanda Bucknum, Thomas Bartlett, Gabriella Composto, Megan Kozlowski, Amanda Walker, Amy Werda, et al. 2012. CD28 ligation increases macrophage suppression of T cell proliferation. Cellular & Molecular Immunology 9(4): 341-349.1672-76812042-0226http://nrs.harvard.edu/urn-3:HUL.InstRepos:10612562When 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 mAb treatment, this “co-suppression” response was due to CD28 ligation increasing the number of IFNγ-secreting cells. Our results illustrate that cellular composition and cytokine milieu influence T cell costimulation biology.en-USCD28CostimulationMacrophagesSuppressionJournal Article2013-05-0810.1038/cmi.2012.13