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

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-gamma and IL-10 as compared with the other pattern characteristic of low Foxp3 expression and predominant production of IL-10 but not IFN-gamma. 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 alpha 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.

• Authors: Jian Hong, Ying C Q Zang, Hong Nie, Jingwu Z Zhang
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 103 Issue 13 Pg. 5024-9 (Mar 28 2006) ISSN: 0027-8424 [Print] United States
• PMID: 16547138 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• Peptide Fragments
• RNA, Messenger
• Receptors, Interleukin-2

Topics

• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cell Line
• Forkhead Transcription Factors (genetics, metabolism)
• Humans
• Multiple Sclerosis (genetics, immunology, metabolism)
• Peptide Fragments (immunology)
• Phenotype
• RNA, Messenger (genetics)
• Receptors, Interleukin-2 (immunology, metabolism)
• Vaccination