Toxoplasma gondii-derived heat shock protein HSP70 functions as a B cell mitogen

Cell Stress Chaperones. 2002 Oct;7(4):357-64. doi: 10.1379/1466-1268(2002)007<0357:tgdhsp>2.0.co;2.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / genetics
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Division / drug effects
  • Cell Division / immunology*
  • Cells, Cultured
  • Female
  • HSP70 Heat-Shock Proteins / immunology*
  • HSP70 Heat-Shock Proteins / pharmacology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / metabolism
  • Male
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Knockout
  • Mice, SCID
  • Mitogens / immunology*
  • Mitogens / pharmacology
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88
  • Polymyxin B / pharmacology
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Toxoplasma / immunology*
  • Toxoplasma / metabolism
  • Toxoplasmosis / immunology*
  • Toxoplasmosis / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • HSP70 Heat-Shock Proteins
  • Homeodomain Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Mitogens
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • RAG-1 protein
  • Polymyxin B

Associated data

  • GENBANK/AB109539