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*
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, United Kingdom;
Department of Parasitology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia;
School of Biological Sciences, University of Manchester, Manchester, United Kingdom; and
§
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
Understanding the basic immunology of an infectious disease
requires insight into the pattern of T cell reactivity and specificity.
Although lymphatic filariasis is a major tropical disease, the
predominant T cell Ags of filarial species such as Brugia
malayi are still undefined. We have now identified a prominent
T cell Ag from B. malayi microfilariae (Mf) as Bm-SPN-2,
a serpin secreted exclusively by this stage. Mf-infected mice mounted
strong, but short-lived, Bm-SPN-2-specific Th1 responses, measured by
in vitro production of IFN-
, but not IL-4 or IL-5, 14 days
postinfection. By day 35, responsiveness to Bm-SPN-2 was lost despite
enhanced reactivity to whole Mf extract. Single immunization with Mf
extract also stimulated typical Th1 reactions to Bm-SPN-2, but IgG1 Ab
responses dominated after repeated immunizations. Human patients
displayed potent humoral responses to Bm-SPN-2 in both IgG1 and IgG4
subclasses. Thus, 100% (20 of 20) of the microfilaremic
(MF+) patients bore IgG4 responses to Bm-SPN-2, while only
30% of endemic normal subjects were similarly positive. Following
chemotherapy, Bm-SPN-2-specific Abs disappeared in 12 of 13
MF+ patients, although the majority remained seropositive
for whole parasite extract. PBMC from most, but not all, endemic
subjects were induced to secrete IFN- when stimulated with Bm-SPN-2.
These findings demonstrate that Bm-SPN-2 is recognized by both murine
and human T and B cells and indicate that their responses are under
relatively stringent temporal control. This study also provides the
first example of a stage-specific secreted molecule that acts as a
major T cell Ag from filarial parasites and is a prime candidate for a
serodiagnostic probe.
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