Regulatory T cells control diabetes without compromising acute anti-viral defense

Clin Immunol. 2014 Aug;153(2):298-307. doi: 10.1016/j.clim.2014.05.006. Epub 2014 May 22.

Abstract

While previous reports have demonstrated the efficacy of regulatory T cell therapy in the prevention of diabetes, systemic immunocompromise and Treg instability remain key safety concerns. Here we examined the influence of induced Treg (iTreg) cell therapy on anti-viral host defense and autoimmune T cell responses during acute viral infection in a murine model of autoimmune diabetes. Protective transfers of iTregs maintained IL-10 expression, expanded in vivo and controlled diabetes, despite losing FoxP3 expression. Adoptive transfer of iTregs affected neither the primary anti-viral CD8 T cell response nor viral clearance, although a significant and sustained suppression of CD4 T cell responses was observed. Following acute viral clearance, iTregs transferred early suppressed both CD4 and CD8 T cell responses, which resulted in the reversion of diabetes. These observations indicate that iTregs suppress local autoimmune processes while preserving the immunocompetent host's ability to combat acute viral infection.

Keywords: Diabetes;; Regulatory T cells;; Safety;; Stability;; Therapy; Viral infection;.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / therapy
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Host-Pathogen Interactions / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Lymphocytic Choriomeningitis / complications
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Lymphocytic choriomeningitis virus / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / transplantation
  • Time Factors
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Green Fluorescent Proteins
  • Interferon-gamma