CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratory syncytial virus in the BALB/c mouse.
CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells. CD40L is critically important for T-B cell and T cell-dendritic cell interactions. CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells. Respiratory syncytial virus (RSV) is an important pathogen of young children and the elderly, which causes bronchiolitis and pneumonia. Studies of mice infected with RSV suggest that a Th2 cytokine response may be responsible for enhanced pulmonary disease. To investigate the effect CD40L has on RSV immunity, mice were infected simultaneously with RSV and either an empty control adenovirus vector or one expressing CD40L or were coimmunized with plasmid DNA vectors expressing CD40L and RSV F and/or G proteins and subsequently challenged with RSV. The kinetics of the intracellular and secreted cytokine responses, the cytotoxic T lymphocyte precursor frequency, NO levels in lung lavage, rates of virus clearance, and anti-RSV Ab titers were determined. These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-gamma) cytokine responses, increases the expression of TNF-alpha and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses. These data suggest that CD40L may have the adjuvant properties needed to optimize the safety and efficacy of RSV vaccines.
Tripp
R A
RA
Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. rgt3@cdc.gov
Jones
L
L
Anderson
L J
LJ
Brown
M P
MP
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000821:virology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019013:CD40 Antigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008562:Membrane Glycoproteins; D014765:Viral Vaccines; D023201:CD40 Ligand; D009569:Nitric Oxide