Abstract
We have investigated the role of Toxoplasma gondii-derived heat shock protein 70 (TgHSP70) as a B cell mitogen by measuring proliferative responses in vitro. TgHSP70 induced prominent proliferative responses in murine B cells derived not only from T gondii-infected but also from uninfected mice. Nude mice responded to TgHSP70; however, severe combined immunodeficiency, RAG1-/- B6, and microMT mice failed to respond. B220+ spleen cells showed marked proliferation after stimulation with TgHSP70, but neither CD4+ nor CD8+ population responded. This unresponsiveness of CD4+ and CD8- T cells to TgHSP70 was antigen presenting cells independent. These data indicate that TgHSP70 induced the proliferation of B cells but not T cells. Polymyxin B, a potent inhibitor of lipopolysaccharide (LPS), did not eliminate TgHSP70-induced proliferation. C3H/HeN mice responded well to TgHSP70 stimulation; however, C3H/HeJ mice carrying a point mutation in the Toll-like receptor (TLR) 4 failed to respond. This indicates that TLR4 is required for TgHSP70-induced B cell activation. The involvement of TLR4 in the TgHSP70-induced proliferative responses of spleen cells was also shown by the use of TLR4-/- mice. But TgHSP70-induced, but not LPS-induced, spleen cell proliferation was observed in MyD88-/- mice, indicating that the MyD88 molecule was involved in LPS-induced proliferation but not in TgHSP70-induced proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antigens, Differentiation / genetics
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology
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Cell Division / drug effects
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Cell Division / immunology*
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Cells, Cultured
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Female
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HSP70 Heat-Shock Proteins / immunology*
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HSP70 Heat-Shock Proteins / pharmacology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / immunology
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / metabolism
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Male
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Inbred ICR
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Mice, Knockout
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Mice, SCID
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Mitogens / immunology*
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Mitogens / pharmacology
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Molecular Sequence Data
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Myeloid Differentiation Factor 88
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Polymyxin B / pharmacology
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Receptors, Cell Surface / deficiency
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Receptors, Cell Surface / genetics
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Receptors, Immunologic / deficiency
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Receptors, Immunologic / genetics
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Toll-Like Receptor 4
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Toll-Like Receptors
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Toxoplasma / immunology*
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Toxoplasma / metabolism
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Toxoplasmosis / immunology*
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Toxoplasmosis / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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HSP70 Heat-Shock Proteins
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Homeodomain Proteins
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Lipopolysaccharides
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Membrane Glycoproteins
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Mitogens
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Cell Surface
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Receptors, Immunologic
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Toll-Like Receptor 4
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Toll-Like Receptors
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RAG-1 protein
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Polymyxin B