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Pathophysiological characteristics of preproinsulin‐specific CD8 + T cells in subjects with juvenile‐onset and adult‐onset type 1 diabetes: A 1‐year follow‐up study
Author(s) -
Paul Mahinder,
Badal Darshan,
Jacob Neenu,
Dayal Devi,
Kumar Rakesh,
Bhansali Anil,
Bhadada Sanjay Kumar,
Sachdeva Naresh
Publication year - 2018
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12536
Subject(s) - medicine , juvenile , pathophysiology , diabetes mellitus , type 1 diabetes , age of onset , endocrinology , pediatrics , disease , genetics , biology
Aims/Hypothesis Among the beta‐cell associated antigens, preproinsulin ( PPI ) has been shown to play a key role in the pathogenesis of type 1 diabetes ( T1D ). PPI ‐specific autoreactive CD8 + T cells emerge early during beta‐cell destruction and persist in peripheral circulation during diabetes progression. However, the influence of insulin therapy on phenotype of autoreactive CD8 + T cells in T1D including, juvenile‐onset T1D ( JOT1D ), and adult‐onset T1D ( AOT1D ) is not yet known. Methods We followed the time course of PPI ‐specific CD8 + T cells in JOT1D and AOT1D subjects that achieved glycemic control after 1 year of insulin therapy, using major histocompatibility complex‐I ( MHC ‐I) dextramers by flow cytometry. Results and Discussion At follow‐up, PPI ‐specific CD8 + T cells could be detected consistently in peripheral blood of all T1D subjects. Proportion of PPI ‐specific effector memory ( T EM ) subsets decreased, while central memory T ( T CM ) cells remained unchanged in both groups. Expression of granzyme‐B and perforin in PPI ‐specific CD8 + T cells also remained unchanged. Further, on analysis of B‐chain and signal peptide ( SP ) specific CD8 + T cell responses separately, we again observed decrease in T EM subset in both the groups, while increase in naive ( T N ) subset was observed in B‐chain specific CD8 + T cells only. Conclusion Our study shows that PPI ‐specific CD8 + T cells can be detected in both JOT1D and AOT1D subjects over a period of time with reliable consistency in frequency but variable pathophysiological characteristics. Insulin therapy seems to reduce the PPI ‐specific T EM subsets; however, the PPI ‐specific T CM cells continue to persist as attractive targets for immunotherapy.