Jl. Vancott et al., Protective immunity to rotavirus shedding in the absence of interleukin-6:Th1 cells and immunoglobulin A develop normally, J VIROLOGY, 74(11), 2000, pp. 5250-5256
We investigated whether interleukin-6 (IL-6) was required for the developme
nt of immunoglobulin A (IgA)- and T-helper 1 (Th1)-associated protective im
mune responses to rotavirus by using adult IL-6-deficient mice [BALB/c and
(C57BL/6 x O1a)F-2 backgrounds]. Naive IL-6(-) mice had normal frequencies
of IgA plasma cells in the gastrointestinal tract. Consistent with this, to
tal levels of IgA in fecal extracts, saliva, and sera were unaltered. In sp
ecific response to oral infection with rhesus rotavirus, IL-6(-) and IL-6() mice exhibited efficient Th1-type gamma interferon responses in Peyer's p
atches, with high levels of serum IgG2a and intestinal Ig4. Although there
was an increase in Th2-type IL-4 in CD4(+) T cells from IL-6(-) mice follow
ing restimulation with rotavirus antigen in the presence of irradiated anti
gen-presenting cells, unfractionated Peger's patch cells failed to produce
a significant increase in IL-4. Moreover, virus-specific IgG1 in serum was
not significantly increased in IG6(-) mice in comparison with IL-6(+) mice.
Following oral inoculation with murine rotavirus, IL-6(-) and IL-6(+) mite
mediated clearance of rotavirus and mounted a strong IgA response. When IL
-6- and IL-6(+) mice [(C57BL/6 x O1a)F-2 background] were orally inoculated
with rhesus rotavirus and later challenged with murine rotavirus, ail of t
he mice maintained high levels of IgA in feces and were protected against r
einfection. Thus, IL-6 failed to provide unique functions in the developmen
t of IgA-secreting B cells and in the establishment of Th1-associated prote
ctive immunity against rotavirus infection in adult mice.