Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d I

Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7608-12. doi: 10.1073/pnas.90.16.7608.

Abstract

T cells control the majority of antigen-specific immune responses. Therefore, influencing the activation of the T-cell response in order to modify immune responsiveness is an obvious therapeutic goal. We have used a mouse model of response to Fel d I, the major cat protein allergen in humans, to explore the ability of peptides derived from Fel d I to inhibit T-cell-dependent immune responses to the peptides themselves and to larger polypeptides. T cells from B6CBAF1 mice respond to the Fel d I peptide IPC-2 after challenge with IPC-2. However, subcutaneous tolerization with IPC-2 prevents this response as measured by production of interleukins 2 and 4 and interferon gamma. Fel d I immunization of B6D2F1 mice results in T-cell responses primarily to one peptide derived from Fel d I. Injecting this peptide in soluble form inhibits T-cell activation (as measured by interleukin 2 production) and antibody production in Fel d I-primed animals when they are subsequently challenged with peptide in adjuvant. Most of the cat-allergic human T-cell response to Fel d I is specific for two peptides on one of its two chains. Immunization of B6CBAF1 mice with recombinant Fel d I chain 1 results in T-cell responses to the same peptides. Subcutaneous administration of these two peptides, which contain some, but not all, of the T-cell epitopes from Fel d I chain I, decreases the T-cell response to the entire recombinant Fel d I chain 1. The ability to tolerize T-cell responses with subcutaneous injections suggests a practical approach to treating human diseases with peptides containing T-cell epitopes.

MeSH terms

  • Allergens / pharmacology*
  • Animals
  • Biological Assay
  • Cats
  • Cell Line
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycoproteins / pharmacology*
  • Immunoglobulin G / biosynthesis
  • Immunosuppression Therapy*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred Strains / immunology*
  • Spleen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Allergens
  • Glycoproteins
  • Immunoglobulin G
  • Interleukin-2
  • Interleukin-4
  • Interferon-gamma
  • Fel d 1 protein, Felis domesticus