An essential role for antibody in neutrophil and eosinophil recruitment to the cornea: B cell-deficient (microMT) mice fail to develop Th2-dependent, helminth-mediated keratitis

J Immunol. 1999 Nov 1;163(9):4970-5.

Abstract

Invasion of the corneal stroma by neutrophils and eosinophils and subsequent degranulation disrupts corneal clarity and can result in permanent loss of vision. In the current study, we used a model of helminth-induced inflammation to demonstrate a novel role for Ab in mediating recruitment of these inflammatory cells to the central cornea. C57BL/6 and B cell-deficient (microMT) mice were immunized s. c. and injected intrastromally with Ags from the parasitic helminth Onchocerca volvulus (which causes river blindness). C57BL/6 mice developed pronounced corneal opacification, which was associated with an Ag-specific IL-5 response and peripheral eosinophilia, temporal recruitment of neutrophils and eosinophils from the limbal vessels to the peripheral cornea and subsequent migration to the central cornea. In contrast, the corneas of microMT mice failed to develop keratitis after intrastromal injection of parasite Ags unless Ags were injected with immune sera. Eosinophils were recruited from the limbal vessels to the peripheral cornea in microMT mice, but failed to migrate to the central cornea, whereas neutrophil recruitment was impaired at both stages. With the exception of IL-5, T cell responses and peripheral eosinophils were not significantly different between C57BL/6 and microMT mice. Taken together, these findings not only demonstrate that Ab is required for the development of keratitis, but also show that recruitment of neutrophils to the cornea is Ab-dependent, whereas eosinophil migration is only partially dependent upon Ab interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Helminth / biosynthesis
  • Antibodies, Helminth / physiology*
  • Antigens, Helminth / administration & dosage
  • Antigens, Helminth / immunology
  • B-Lymphocytes / pathology*
  • Chemotaxis, Leukocyte / genetics
  • Chemotaxis, Leukocyte / immunology
  • Cornea / immunology*
  • Cornea / pathology
  • Eosinophilia / immunology
  • Eosinophils / immunology*
  • Eosinophils / pathology
  • Immune Sera / physiology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin mu-Chains / genetics
  • Injections
  • Keratitis / genetics
  • Keratitis / immunology*
  • Keratitis / pathology
  • Lymphopenia / genetics*
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration / genetics
  • Neutrophil Infiltration / immunology*
  • Onchocerca volvulus / immunology
  • Onchocerciasis, Ocular / genetics
  • Onchocerciasis, Ocular / immunology*
  • Onchocerciasis, Ocular / pathology
  • Stromal Cells / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Antibodies, Helminth
  • Antigens, Helminth
  • Immune Sera
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin mu-Chains