Vaccination with selected synovial T cells in rheumatoid arthritis

Arthritis Rheum. 2007 Feb;56(2):453-63. doi: 10.1002/art.22316.

Abstract

Objective: This pilot clinical study was undertaken to investigate the role of T cell vaccination in the induction of regulatory immune responses in patients with rheumatoid arthritis (RA).

Methods: Autologous synovial T cells were selected for pathologic relevance, rendered inactive by irradiation, and used for vaccination. Fifteen patients received T cell vaccination via 6 subcutaneous inoculations over a period of 12 months.

Results: T cell vaccination led to induction of CD4+ Tregs and CD8+ cytotoxic T cells specific for T cell vaccine. There was selective expansion of CD4+,V(beta)2+ Tregs that produced interleukin-10 (IL-10) and expressed a high level of transcription factor Foxp3, which coincided with depletion of overexpressed BV14+ T cells in treated patients. CD4+ IL-10-secreting Tregs induced by T cell vaccination were found to react specifically with peptides derived from IL-2 receptor alpha-chain. The expression level of Foxp3 in CD4+ T cells and increased inhibitory activity of CD4+,CD25+ Tregs were significantly elevated following T cell vaccination. The observed regulatory immune responses collectively correlated with clinical improvement in treated patients. In an intent-to-treat analysis, a substantial response, defined as meeting the American College of Rheumatology 50% improvement criteria, was shown in 10 of the 15 patients (66.7%) and was accompanied by a marked improvement in RA-related laboratory parameters.

Conclusion: These findings suggest that T cell vaccination induces regulatory immune responses that are associated with improved clinical and laboratory variables in RA patients.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation
  • Humans
  • Immunotherapy, Active / methods
  • Immunotherapy, Active / trends
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Male
  • Middle Aged
  • Pilot Projects
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / physiology
  • Synovial Membrane / immunology*
  • Synovial Membrane / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Vaccination / methods*

Substances

  • CD4 Antigens
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Antigen, T-Cell