@article {542161,
	title = {CD28 ligation increases macrophage suppression of T-cell proliferation.},
	journal = {Cell Mol Immunol},
	volume = {9},
	number = {4},
	year = {2012},
	month = {2012 Jul},
	pages = {341-9},
	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 {\textquoteright}cosuppression{\textquoteright} 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.},
	keywords = {Animals, Antigens, CD28, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cellular Microenvironment, Immunosuppression, Interferon-gamma, Macrophages, Peritoneal, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type II, Receptor Aggregation, Receptor Cross-Talk, T-Lymphocytes},
	issn = {2042-0226},
	doi = {10.1038/cmi.2012.13},
	author = {Silberman, Daniel and Bucknum, Amanda and Bartlett, Thomas and Composto, Gabriella and Kozlowski, Megan and Walker, Amanda and Werda, Amy and Cua, Jackelyn and Sharpe, Arlene H and Somerville, John E and Riggs, James E}
}
