Cord blood CD4+ T cells respond to self heat shock protein 60 (HSP60) |
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Authors: | Aalberse Joost A Kapitein Berber de Roock Sytze Klein Mark R de Jager Wilco van der Zee Ruurd Hoekstra Maarten O van Wijk Femke Prakken Berent J |
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Affiliation: | Department of Pediatric Immunology, Wilhelmina Children's Hospital, Utrecht, The Netherlands. jaalber2@umcutrecht.nl |
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Abstract: | BackgroundTo prevent harmful autoimmunity most immune responses to self proteins are controlled by central and peripheral tolerance. T cells specific for a limited set of self-proteins such as human heat shock protein 60 (HSP60) may contribute to peripheral tolerance. It is not known whether HSP60-specific T cells are present at birth and thus may play a role in neonatal tolerance. We studied whether self-HSP60 reactive T cells are present in cord blood, and if so, what phenotype these cells have.Methodology/Principal FindingsCord blood mononuclear cells (CBMC) of healthy, full term neonates (n = 21), were cultured with HSP60 and Tetanus Toxoid (TT) to study antigen specific proliferation, cytokine secretion and up-regulation of surface markers. The functional capacity of HSP60-induced T cells was determined with in vitro suppression assays. Stimulation of CBMC with HSP60 led to CD4+ T cell proliferation and the production of various cytokines, most notably IL-10, Interferon-gamma, and IL-6. HSP60-induced T cells expressed FOXP3 and suppressed effector T cell responses in vitro.ConclusionSelf-reactive HSP60 specific T cells are already present at birth. Upon stimulation with self-HSP60 these cells proliferate, produce cytokines and express FOXP3. These cells function as suppressor cells in vitro and thus they may be involved in the regulation of neonatal immune responses. |
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