CD40 ligand (CD154) enhances the Th1 and antibody responses to respiratorysyncytial virus in the BALB/c mouse

CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed main ly by activated T cells. CD40L is critically important for T-B cell and T c ell-dendritic cell interactions. CD40L expression promotes Th1 cytokine res ponses to protein Ags and is responsible for Ig isotype switching in B cell s. Respiratory syncytial virus (RSV) is an important pathogen of young chil dren and the elderly, which causes bronchiolitis and pneumonia, Studies of mice infected with RSV suggest that a Th2 cytokine response may be responsi ble for enhanced pulmonary disease. To investigate the effect CD40L has on RSV immunity, mice were infected simultaneously with RSV and either an empt y control adenovirus vector or one expressing CD40L or were coimmunized wit h plasmid DNA vectors expressing CD40L and RSV F and/or G proteins and subs equently challenged with RSV, The kinetics of the intracellular and secrete d cytokine responses, the cytotoxic T lymphocyte precursor frequency, NO le vels 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 adjuvan t properties needed to optimize the safety and efficacy of RSV vaccines.