Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHCclass II-restricted responses
Th. Ermak et al., Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHCclass II-restricted responses, J EXP MED, 188(12), 1998, pp. 2277-2288
We examined the roles of cell- and antibody-mediated immunity in urease vac
cine-induced protection against Helicobacter pylori infection. Normal and k
nockout mice deficient major histocompatibility complex (MHC) class I, MHC
class II, or B cell responses were mucosally immunized with urease plus Esc
herichia coli heat-labile enterotoxin (LT), or parenterally immunized with
urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H.
pylori strain X47-2AL, and H. pylori organsims and leukocyte infiltration
in the gastric mucosa quantified. In an adjuvant/route study in normal mice
, there was a direct correlation between the level of protection and the de
nsity of T cells recruited to the gastric mucosa. In knockout studies, oral
immunization with urease plus LT protected MHC class I knockout mice [beta
(2)-microglobulin (-/-)] but not MHC class II knockout mice [I-A(b) (-/-)].
In B cell knockout mice [mu MT (-/-)], vaccine-induced protection was equi
valent to the observed in immunized wild-type (+/+) mice; no IgA(+) cells w
ere detected in the stomach, but levels of CD4(+) cells equivalent to those
in the wild-type strain (+/+) were seen. These studies indicate that prote
ction of mice against H. pylori infection by immunization with the urease a
ntigen is dependent on MHC class II-restricted, cell mediated mechanisms, a
nd antibody response to urease are not required for protection.