title: Role of B7 costimulatory molecules in the adjuvant activity of the heat-labile enterotoxin of Escherichia coli.
abstract: Much interest has been directed at understanding the adjuvant properties of the heat-labile enterotoxin of Escherichia coli (LT). In this study, we have assessed how LT compared with the nonenzymatic mutant LT (E112K) affect the level of B7-1 and B7-2 expression on APCs, and we determined how these costimulatory molecules influence their adjuvant properties. Analysis of B7-1 and B7-2 expression on B cells revealed that LT enhanced B7-2 but not B7-1, while LT (E112K) had no effect on the expression of either costimulatory molecule. Treatment of macrophage or dendritic cells with LT resulted in a predominant enhancement of B7-2, while LT (E112K) induced mainly B7-1 expression. Analysis of LT- and LT (E112K)-treated B cells, macrophage, and dendritic cells also revealed significant differences in their ability to enhance anti-CD3-stimulated CD4(+) T cell proliferative responses via B7-1 and B7-2. Furthermore, the ability of LT to enhance both Ab and CD4(+) T cell responses to a coadministered Ag was severely abrogated in B7-2- but not B7-1-deficient mice. In contrast, the in vivo adjuvant properties of LT (E112K) appeared to be mediated by both B7-1 and B7-2 for optimal CD4(+) T cell responses, while B7-1 appeared to be the predominant B7 molecule involved in the ability of LT (E112K) to augment Ab responses to a coadministered Ag. These findings demonstrate distinct differences in the ability of LT and LT (E112K) to enhance B7-1 and B7-2 on APC, as well as a dependence upon these costimulatory molecules for their adjuvant properties.
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
authors.forename: Arlene
authors.initials: A
authors.lastname: Sharpe
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Michalek
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D051940:B7-2 Antigen; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D029968:Escherichia coli Proteins; D016167:Integrin alphaXbeta2 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017354:Point Mutation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001427:Bacterial Toxins; C497965:Cd86 protein, mouse; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; C027538:heat-labile enterotoxin, E coli; D017493:Leukocyte Common Antigens