The Serpin Secreted by Brugia malayi Microfilariae, Bm-SPN-2, Elicits Strong, but Short-Lived, Immune Responses in Mice and Humans

• Published in: The Journal of immunology (1950) Vol. 165; no. 9; pp. 5161 - 5169
• Main Authors: Zang, Xingxing, Atmadja, Agnes Kurniawan, Gray, Paul, Allen, Judith E, Gray, Carolyn A, Lawrence, Rachel A, Yazdanbakhsh, Maria, Maizels, Rick M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.11.2000
• Subjects: Animals; Antigens, Differentiation, T-Lymphocyte - administration & dosage; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - isolation & purification; Antigens, Helminth - administration & dosage; Antigens, Helminth - immunology; Antigens, Helminth - isolation & purification; Antigens, Helminth - metabolism; Bm-SPN-2 antigen; Brugia malayi; Brugia malayi - enzymology; Brugia malayi - growth & development; Brugia malayi - immunology; Cells, Cultured; Cloning, Molecular; Dose-Response Relationship, Immunologic; Female; Filariasis - drug therapy; Filariasis - immunology; Filariasis - parasitology; Helminth Proteins; Humans; Immunoglobulin G - biosynthesis; Immunoglobulin G - blood; Immunoglobulin G1; Immunoglobulin G4; Immunoglobulin Isotypes - biosynthesis; Immunoglobulin Isotypes - blood; Interferon-gamma - biosynthesis; Interferon-gamma - blood; Interferon-gamma - metabolism; Interleukin-5 - biosynthesis; Lymphocyte Activation - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Microfilariae - enzymology; Microfilariae - growth & development; Microfilariae - immunology; serpins; Serpins - administration & dosage; Serpins - immunology; Serpins - isolation & purification; Serpins - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.9.5161

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.