The type of responder T-cell has a significant impact in a human in vitro suppression assay |
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Authors: | Jana Srikanta Campbell Hope Woodliff Jeffrey Waukau Jill Jailwala Parthav Ghorai Jugal Ghosh Soumitra Glisic Sanja |
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Institution: | Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America. |
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Abstract: | BackgroundIn type 1 diabetes (T1D), a prototypic autoimmune disease, effector T cells destroy beta cells. Normally, CD4+CD25+high, or natural regulatory T cells (Tregs), counter this assault. In autoimmunity, the failure to suppress CD4+CD25low T cells is important for disease development. However, both Treg dysfunction and hyperactive responder T-cell proliferation contribute to disease.Methods/Principal FindingsWe investigated human CD4+CD25low T cells and compared them to CD4+CD25- T cells in otherwise equivalent in vitro proliferative conditions. We then asked whether these differences in suppression are exacerbated in T1D. In both single and co-culture with Tregs, the CD4+CD25low T cells divided more rapidly than CD4+CD25- T cells, which manifests as increased proliferation/reduced suppression. Time-course experiments showed that this difference could be explained by higher IL-2 production from CD4+CD25low compared to CD4+CD25- T cells. There was also a significant increase in CD4+CD25low T-cell proliferation compared to CD4+CD25- T cells during suppression assays from RO T1D and at-risk subjects (n?=?28, p?=?0.015 and p?=?0.024 respectively).Conclusions/SignificanceThe in vitro dual suppression assays proposed here could highlight the impaired sensitivity of certain responder T cells to the suppressive effect of Tregs in human autoimmune diseases. |
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