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 pathogens in the mucosal compartment. Using mice with a targeted disruption in IgA 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 subtype 1) and neuraminidase (neuraminidase subtype 1) vaccine in the absence of adjuvant were found to be more susceptible to influenza virus infection than IgA(+/+) mice (13 vs 75% survival after virus challenge). Inclusion of IL-12 during immunization restored the protective efficacy of the vaccine to that seen in IgA(+/+) animals. IgA(-/-) mice had no detectable IgA expression, but displayed enhanced serum and pulmonary IgM and IgG Ab levels after IL-12 treatment. Assessment of T cell function revealed markedly depressed splenic lymphoproliferative responses to PHA in IgA(-/-) animals compared with IgA(+/+) mice. Furthermore, IgA(-/-) animals displayed impaired T cell priming to the H1N1 subunit vaccine, with concomitant reduction in recall memory responses due to a defect in APC function. Collectively, these results provide evidence that a major role of IgA is to facilitate presentation of Ag to mucosal T cells. IL-12 treatment can overcome IgA deficiency by providing adequate T cell priming during vaccination.
Arulanandam
B P
BP
Center for Immunology and Microbial Disease Research, Albany Medical College, Albany, NY 12208, USA.
Raeder
R H
RH
Nedrud
J G
JG
Bucher
D J
DJ
Le
J
J
Metzger
D W
DW
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D015707:HN Protein / Q000008:administration & dosage / Q000276:immunology; D017098:IgA Deficiency / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007156:Immunologic Memory / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018664:Interleukin-12 / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D000914:Antibodies, Viral; D015707:HN Protein; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D018664:Interleukin-12