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Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; and
Cell and Gene Therapy Program, St. Jude Children’s Research Hospital, Memphis, TN 38101
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-
) cytokine responses,
increases the expression of TNF-
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.
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