M. Korenaga et al., Impaired protective immunity and T helper 2 responses in alymphoplasia (aly) mutant mice infected with Trichinella spiralis, IMMUNOLOGY, 102(2), 2001, pp. 218-224
The alymphoplasia (aly) mutation of mice prevents the development of system
ic lymph nodes and Peyer's patches. The mutant homozygotes (alylaly) are pa
rtially deficient in both humoral and cell-mediated immune functions. In th
e present study, we show that adult worm expulsion was slightly delayed and
that T helper 2 (Th2)-type responses were partially defective in alylaly.
mice after infection with Trichinella spiralis. Male alylaly and alyl+ mice
(8-weeks old) were infected with 400 muscle larvae. There was no differenc
e in worm recovery between the two groups on day 5. However, worm recovery
in alylaly mice was significantly higher than that in alyl+ mice on day 14,
Mucosal mast cells increased in number and peaked 14 days after infection
in alyl+ mice, alylaly mice were deficient in their mucosal mast cell respo
nse through out the primary infection. To examine the existence of mast cel
l precursors, alylaly mice were treated with recombinant interleukin-3 (rIL
-3) before infection. The mast cell response was poorly induced in alylaly
mice treated with rIL-3. An immunoglobulin E (IgE) response was not detecte
d in alylaly mice during the course of infection. Serum IgG1 levels in alyl
aly mice were significantly lower than that of alyl+. The serum IgG2a level
s increased in both strains of mice. However. IgG2a production in alylaly m
ice on day 14 was half as much as that in alyl + mice. Stimulation of splen
ic T cells in vitro with anti-CD3 monoclonal antibody (mAb) showed that spl
een cells from alyl+ mice on day 5 produced more IL-4 than spleen cells fro
m alylaly mice. IL-4 production from alylaly mice on day 14 was half that f
rom alyl+ mice. Interferon-gamma (IFN-gamma) was produced in both alylaly a
nd alyl+ mice on day 14. Proliferation assay showed that T cells of alylaly
mice responded poorly when cultured with antigen-presenting cells. These r
esults suggest that aly gene is needed for the induction of protective immu
nity and Th2 responses in mice infected with T. spiralis.