CD40 Ligand (CD154) Enhances the Th1 and Antibody Responses to Respiratory Syncytial Virus in the BALB/c Mouse

Abstract

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-γ) cytokine responses, increases the expression of TNF-α 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.

Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- MacrophageColony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles

“…CD40L chimeric SIV VLPs were very efficient in stimulating robust CD4 ϩ -and CD8 ϩ -T-cell responses. Our findings on the induction of T-cell responses by CD40L are consistent with previously published studies (32,46,49). However, CD40L SIV VLPs did not induce enhanced SIV-Env specific serum IgG levels even after three immunizations; the levels were comparable to those found with control SIV VLPs.…”

“…Another immunostimulatory molecule is CD40 ligand (CD40L), which is a surface molecule primarily expressed on mature CD4 ϩ T cells. Interaction between CD40L and CD40 is important for T-cell-dependent B-cell activation and isotype switching (5,49). Binding of CD40L to CD40 modulates the cellular immune responses by inducing interleukin 12 (IL-12) production and expression of costimulatory molecules residing on antigen-presenting cells (APCs).…”

Selective Requirement for CD40-CD154 in Drug-Induced Type 1 Versus Type 2 Responses to Trinitrophenyl-Ovalbumin

“…Studies using CD154-deficient mice or various autoimmune, infection, and transplant models have shown that CD40-mediated costimulation is involved in both type 1 and type 2 responses. However, results concerning the particular requirement for CD40-mediated costimulation in both responses are contradictory (7,(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

“…Blocking of CD154 in NOD/shi mice also impaired the development of isletreactive Th1 cells (7). Moreover, the CD40-CD154 interaction was demonstrated to be crucial for in vivo priming of Th1 cells by IL-12-producing APC in SJL/J mice (21), and supplementary expression of CD154 directs the response to respiratory syncytial virus toward a type 1 phenotype (22). At last, anti-CD154 Ab was found to induce tolerance to 2,4-dinitrofluorobenzene-induced contact hypersensitivity, a typical type 1 phenomenon (23), but CD154-deficient mice showed normal delayed-type hypersensitivity responses to OVA (24).…”

Cloning, sequence analysis and expression of ovine CD154 (CD40 ligand)

“…The expression of CD154 appeared to enhance both immune responses and disease protection (Mendoza et al, 1997, Gurunathan et al, 1998, Tripp et al, 2000. Some studies have shown that co administration of plasmid encoded bovine CD154 enhanced antibody responses to bovine herpesvirus I glycoprotein D in sheep (Manoj et al, 2003).…”