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The Serpin Secreted by Brugia malayi Microfilariae, Bm-SPN-2, Elicits Strong, but Short-Lived, Immune
 

Summary: The Serpin Secreted by Brugia malayi Microfilariae,
Bm-SPN-2, Elicits Strong, but Short-Lived, Immune
Responses in Mice and Humans1
Xingxing Zang,2
* Agnes Kurniawan Atmadja,
Paul Gray,* Judith E. Allen,* Carolyn A. Gray,
Rachel A. Lawrence,
Maria Yazdanbakhsh,
and Rick M. Maizels3
*
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,

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine