CD4+ regulatory T cell responses induced by T cell vaccination in patients with multiple sclerosis

doi:10.1073/pnas.0508784103

CD4⁺ regulatory T cell responses induced by T cell vaccination in patients with multiple sclerosis

^†Department of Neurology, Baylor College of Medicine, Houston, TX 77030;
^‡Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China; and
^§E-Institute of Shanghai Universities, Shanghai 200025, China

Edited by Hugh O. McDevitt, Stanford University School of Medicine, Stanford, CA, and approved February 2, 2006 (received for review October 6, 2005)

Abstract

Immunization with irradiated autologous T cells (T cell vaccination) is shown to induce regulatory T cell responses that are poorly understood. In this study, CD4⁺ regulatory T cell lines were generated from patients with multiple sclerosis that received immunization with irradiated autologous myelin basic protein-reactive T cells. The resulting CD4⁺ regulatory T cell lines had marked inhibition on autologous myelin basic protein-reactive T cells and displayed two distinctive patterns distinguishable by the expression of transcription factor Foxp3 and cytokine profile. The majority of the T cell lines had high Foxp3 expression and secreted both IFN-γ and IL-10 as compared with the other pattern characteristic of low Foxp3 expression and predominant production of IL-10 but not IFN-γ. CD4⁺ regulatory T cell lines of both patterns expressed CD25 and reacted with activated autologous T cells but not resting T cells, irrespective of antigen specificity of the target T cells. It was evident that they recognized preferentially a synthetic peptide corresponding to residues 61–73 of the IL-2 receptor α chain. T cell vaccination correlated with increased Foxp3 expression and T cell reactivity to peptide 61–73. The findings have important implications in the understanding of the role of CD4⁺ regulatory T cell response induced by T cell vaccination.

Footnotes

^¶To whom correspondence should be addressed at:
Baylor College of Medicine, Mail Station NB302, One Baylor Plaza, Houston, TX 77030.
E-mail: jzang{at}bcm.tmc.edu
Author contributions: Y.C.Q.Z. and J.Z.Z. designed research; J.H. and H.N. performed research; and J.Z.Z. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

ELISPOT,

enzyme-linked immunospot;

MBP,

myelin basic protein;

MS,

multiple sclerosis;

PBMC,

peripheral blood mononuclear cell.