IgA immunodeficiency leads to inadequate Th cell priming and increased susceptibility to influenza virus infection

IgA is considered to be the principal Ab involved in defense against pathog ens in the mucosal compartment, Using mice with a targeted disruption in Ig A gene expression (IgA(-/-) mice), we have examined the precise role of IgA in protective anti-influenza responses after intranasal vaccination, IgA(- /-) mice immunized intranasally with soluble hemagglutinin (hemagglutinin s ubtype 1) and neuraminidase (neuraminidase subtype 1) vaccine in the absenc e of adjuvant were found to be more susceptible to influenza virus infectio n than IgA(+/+) mice (13 vs 75% survival after virus challenge). Inclusion of IL-12 during immunization restored the protective efficacy of the vaccin e to that seen in IgA(+/+) animals, IgA(-/-) mice had no detectable IgA exp ression, but displayed enhanced serum and pulmonary IgM and IgG Ab levels a fter IL-12 treatment. Assessment of T cell function revealed markedly depre ssed splenic lymphoproliferative responses to PHA in IgA(-/-) animals compa red with IgA(+/+) mice. Furthermore, IgA(-/-) animals displayed impaired T cell priming to the H1N1 subunit vaccine, with concomitant reduction in rec all memory responses due to a defect in APC function. Collectively, these r esults provide evidence that a major role of IgA is to facilitate presentat ion of Ag to mucosal T cells. IL-12 treatment can overcome IgA deficiency b y providing adequate T cell priming during vaccination.