CD4+ regulatory T cell responses induced by T cell vaccination in patients with multiple sclerosis.
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.
Hong
Jian
J
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Zang
Ying C Q
YC
Nie
Hong
H
Zhang
Jingwu Z
JZ
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D010446:Peptide Fragments; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2