title: Studies on the interdependence of gp39 and B7 expression and function during antigen-specific immune responses.
abstract: Interactions between T and B cells are dynamic and regulated by interacting receptor: co-receptors. Interactions between CD40 and its ligand, gp39, and the CD28/CTLA-4 and B7 family members play a decisive role in regulating the progression of cognate interactions. The interdependence of gp39-CD40 and CD28/CTLA-B7 expression and function was studied in vitro during an antigen-induced immune response using T cells from mice expressing a transgenic T cell receptor (TCR). gp39 was induced on pigeon cytochrome c (PCC)-transgenic T cells in the presence of antigen and antigen-presenting cells. The antigen-induced expression of gp39 on transgenic T cells was inhibited by antibodies to class II major histocompatibility complex, CD4 and LFA-1, but not by CTLA-4 Ig, anti-B7-1 or anti-B7-2. These data established that the antigen-induced expression of gp39 was not dependent on co-stimulation via CD28/CTLA-4. The addition of PCC also resulted in the modest expression of B7-1 and a more robust expression of B7-2 on the cognate B cells. The addition of anti-gp39 blocked the up-regulated expression of B7-1 and partially blocked the up-regulated expression of B7-2. The addition of anti-gp39 and anti-interleukin-4 inhibited antigen-induced expression of B7-2 on B cells to near background levels. Studies on the up-regulation of B7-1 and B7-2 on resting B cells showed that soluble gp39 up-regulated B7-1 and B7-2 expression on B cells. In addition, interleukin-4 and interferon-gamma up-regulated B7-2 expression on B cells. Taken together, these data demonstrate that the antigen-induced expression of gp39 is dependent on TCR-derived signals, yet independent of CD28/CTLA-4 co-stimulatory signals. Cognate interactions also resulted in the modest enhancement of B7-1 expression and a more profound expression of B7-2 which were completely or partially dependent on gp39-CD40 interactions.
authors.affiliation: Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756.
authors.forename: M
authors.initials: M
authors.lastname: Roy
authors.forename: A
authors.initials: A
authors.lastname: Aruffo
authors.forename: J
authors.initials: J
authors.lastname: Ledbetter
authors.forename: P
authors.initials: P
authors.lastname: Linsley
authors.forename: M
authors.initials: M
authors.lastname: Kehry
authors.forename: R
authors.initials: R
authors.lastname: Noelle
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D018122:B7-1 Antigen / Q000032:analysis* / Q000502:physiology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D018796:Immunoconjugates; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D000069594:Abatacept