title: CD28 ligation increases macrophage suppression of T-cell proliferation.
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.
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Silberman
authors.forename: Amanda
authors.initials: A
authors.lastname: Bucknum
authors.forename: Thomas
authors.initials: T
authors.lastname: Bartlett
authors.forename: Gabriella
authors.initials: G
authors.lastname: Composto
authors.forename: Megan
authors.initials: M
authors.lastname: Kozlowski
authors.forename: Amanda
authors.initials: A
authors.lastname: Walker
authors.forename: Amy
authors.initials: A
authors.lastname: Werda
authors.forename: Jackelyn
authors.initials: J
authors.lastname: Cua
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: John E
authors.initials: JE
authors.lastname: Somerville
authors.forename: James E
authors.initials: JE
authors.lastname: Riggs
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011940:Receptor Aggregation / Q000276:immunology; D020239:Receptor Cross-Talk; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II