CD30 discriminates heat shock protein 60-induced FOXP3+ CD4+ T cells with a regulatory phenotype.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Ismé de KleerBerent Prakken

Abstract

In many animal models, the manifestations of inflammatory diseases can be prevented by the adoptive transfer of CD4(+)FOXP3(+) regulatory T cells (Tregs). CD4(+)FOXP3(+) Tregs can be obtained by isolation and expansion of polyclonal naturally occurring Tregs or by Ag-specific activation of CD4(+)CD25(-)FOXP3(-) T cells. Two major obstacles are hampering the translation of this latter protocol into therapeutic application. First, there is a lack of knowledge on relevant autoantigens. Second, the resulting population is contaminated with activated CD4(+) T cells that transiently express Forkhead box P3 but gain no regulatory function. Therefore, these cells may not be safe for clinical application. In this study, we demonstrate that highly suppressive FOXP3(+) Tregs can be induced in vitro by the activation of CD4(+)CD25(-) T cells with the self-Ag human 60-kDa heat shock protein (HSP60). The activation induced suppressive FOXP3(+) Tregs can be distinguished by surface expression of CD30 from nonsuppressive FOXP3(+) effector cells. We confirm that the induced CD30(+)FOXP3(+) Tregs recognize HSP60 epitopes and that the induction of Tregs by HSP60 is enhanced by signaling via TLR4 on APCs. These findings have implications for the g...Continue Reading

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Citations

Aug 8, 2012·Cell Stress & Chaperones·Berber KapiteinBerent J Prakken
Jun 28, 2012·Clinical & Developmental Immunology·Bo JinAnthony E T Yeo
Sep 21, 2011·PloS One·Joost A AalberseBerent J Prakken
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Jul 9, 2013·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Xiang-Yang Wang, John R Subjeck
Jul 23, 2014·Oncoimmunology·Monica RodolfoLicia Rivoltini
Dec 4, 2012·Clinical and Experimental Immunology·E Zonneveld-HuijssoonF van Wijk
Jan 30, 2018·Current Medicinal Chemistry·Alexey V BaldinLyudmila V Savvateeva

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