The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans

Xingxing Zang, A. K. Atmadja, P. Gray, J. E. Allen, C. A. Gray, R. A. Lawrence, M. Yazdanbakhsh, R. M. Maizels

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Abstract

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-γ, 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-γ 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.

Original languageEnglish (US)
Pages (from-to)5161-5169
Number of pages9
JournalJournal of Immunology
Volume165
Issue number9
StatePublished - Nov 1 2000
Externally publishedYes

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Brugia malayi
Serpins
Microfilariae
Immunoglobulin G
T-Lymphocytes
Immunization
Parasites
T-Cell Antigen Receptor Specificity
Filarial Elephantiasis
Interleukin-5
Allergy and Immunology
Interleukin-4
Communicable Diseases
B-Lymphocytes
Drug Therapy

ASJC Scopus subject areas

  • Immunology

Cite this

Zang, X., Atmadja, A. K., Gray, P., Allen, J. E., Gray, C. A., Lawrence, R. A., ... Maizels, R. M. (2000). The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans. Journal of Immunology, 165(9), 5161-5169.

The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans. / Zang, Xingxing; Atmadja, A. K.; Gray, P.; Allen, J. E.; Gray, C. A.; Lawrence, R. A.; Yazdanbakhsh, M.; Maizels, R. M.

In: Journal of Immunology, Vol. 165, No. 9, 01.11.2000, p. 5161-5169.

Research output: Contribution to journalArticle

Zang, X, Atmadja, AK, Gray, P, Allen, JE, Gray, CA, Lawrence, RA, Yazdanbakhsh, M & Maizels, RM 2000, 'The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans', Journal of Immunology, vol. 165, no. 9, pp. 5161-5169.
Zang, Xingxing ; Atmadja, A. K. ; Gray, P. ; Allen, J. E. ; Gray, C. A. ; Lawrence, R. A. ; Yazdanbakhsh, M. ; Maizels, R. M. / The serpin secreted by Brugia malayi microfilariae, Bm-SPN-2, elicits strong, but short-lived, immune responses in mice and humans. In: Journal of Immunology. 2000 ; Vol. 165, No. 9. pp. 5161-5169.
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abstract = "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-γ, 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-γ 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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AU - Atmadja, A. K.

AU - Gray, P.

AU - Allen, J. E.

AU - Gray, C. A.

AU - Lawrence, R. A.

AU - Yazdanbakhsh, M.

AU - Maizels, R. M.

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