CD28 ligation increases macrophage suppression of T-cell proliferation

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)-c-secreting cells. Our results illustrate that cellular composition and cytokine milieu influence T-cell costimulation biology. Cellular & Molecular Immunology (2012) 9, 341-349; doi: 10.1038/ cmi. 2012.13; published online 23 April 2012