title: B7-H1 expression on old CD8+ T cells negatively regulates the activation of immune responses in aged animals.
abstract: T cell responses are compromised in the elderly. The B7-CD28 family receptors are critical in the regulation of immune responses. We evaluated whether the B7-family and CD28-family receptors were differentially expressed in dendritic cells, macrophages, and CD4(+) and CD8(+) T cells from young and old mice, which could contribute to the immune dysfunction in the old. Although most of the receptors were equally expressed in all cells, >85% of the old naive CD8(+) T cells expressed B7-H1 compared with 25% in the young. Considering that B7-H1 negatively regulates immune responses, we hypothesized that expression of B7-H1 would downregulate the function of old CD8(+) T cells. Old CD8(+) T cells showed reduced ability to proliferate, but blockade of B7-H1 restored the proliferative capacity of old CD8(+) T cells to a level similar to young CD8(+) T cells. In vivo blockade of B7-H1 restored antitumor responses against the B7-H1(-) BM-185-enhanced GFP tumor, such that old animals responded with the same efficiency as young mice. Our data also indicate that old CD8(+) T cells express lower levels of TCR compared with young CD8(+) T cells. However, following antigenic stimulation in the presence of B7-H1 blockade, the levels of TCR expression were restored in old CD8(+) T cells, which correlated with stronger T cell activation. These studies demonstrated that expression of B7-H1 in old CD8(+) T cells impairs the proper activation of these cells and that blockade of B7-H1 could be critical to optimally stimulate a CD8 T cell response in the old.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259.
authors.forename: Noweeda
authors.initials: N
authors.lastname: Mirza
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259.
authors.forename: Maria Adelaida
authors.initials: MA
authors.lastname: Duque
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259.
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Dominguez
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Rochester, Rochester, MN 55905.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Schrum
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Rochester, Rochester, MN 55905.
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lustgarten
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000502:physiology; D060890:B7-H1 Antigen; D018106:CD28 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor
chemical_list: D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D018106:CD28 Antigens; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor