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

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

Research output: Contribution to journalArticlepeer-review

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-gamma, 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-gamma 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
Pages (from-to)5161-9
Number of pages9
JournalJournal of Immunology
Volume165
Issue number9
Publication statusPublished - 2000

Keywords

  • Animals
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Helminth
  • Brugia malayi
  • Cells, Cultured
  • Cloning, Molecular
  • Dose-Response Relationship, Immunologic
  • Female
  • Filariasis
  • Helminth Proteins
  • Humans
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Interferon-gamma
  • Interleukin-5
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Microfilaria
  • Serpins
  • T-Lymphocytes

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