Wj. Dai et al., Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of alpha beta(+) CD4(+) T cells, INFEC IMMUN, 69(10), 2001, pp. 6074-6083
Echinococcus multilocularis causes alveolar echinococcosis, one of the most
lethal helminthic (accidental) infections in humans, as the life cycle pre
dominantly includes wildlife rodents as intermediate hosts. The physical ba
rrier between the proliferating parasitic metacestode and the host tissue i
s the acellular laminated layer (LL), which is characterized by its rich hi
gh-molecular-weight polysaccharide composition. Conversely to a crude prote
in-rich vesicular fluid antigen, a major carbohydrate antigen of the LL-the
Em2(G11) antigen-did not stimulate murine T-cell proliferation in vitro. I
n fact, the persistent metacestode growth and antigenic stimulation induced
a Th2 shift in vivo following conventional infection by intraperitoneal in
oculation of 100 metacestode vesicles into C57/BL6 mice. Concurrently, the
expression of Th1 cytokines (interleukin-2 and gamma interferon) remained p
ersistently low until the late stage of chronic infection. In comparison to
a recombinant proteinic II/3 antigen, the specific immunoglobulin G (IgG)
response against the Em2(G11) antigen (including all IgG isotypes) maintain
ed persistently low avidity. Furthermore, the Em2(G11) antigen induced a sp
ecific IgM and IgG response in T-cell-deficient athymic nude, TCR beta (-/-
), major histocompatibility complex class II (MHCII)(-/-)(CD4-deficient), a
nd CD40(-/-) mice. The Em2(G11)-specific IgG synthesized in nude TCR beta (
-/-) and MHCII-/- mice was predominantly of the IgG3 and IgG2a isotypes and
of the IgG3 and IgG2b isotypes in CD40(-/-) mice. This finding suggested t
hat in vivo, the IgG response to major carbohydrate antigen Em2(G11) of E.
multilocularis could take place independently of alpha beta (+) CD4(+) T ce
lls and in the absence of CD40-CD40 ligand interactions; thus, the Em2(G11)
antigen of the acellular LL represents a T-cell-independent antigen. Funct
ionally, the encapsulating LL, and especially its major carbohydrate antige
n, Em2(G11), seems to be one of the key factors in the parasite's survival
strategy and acts by modulating the host immune response by virtue of its T
-cell-independent nature.