Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation

Elsa Laughlin; George Burke; Alberto Pugliese; Ben Falk; Gerald Nepom

doi:10.1016/j.clim.2008.03.459

Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation

Elsa Laughlin, George Burke, Alberto Pugliese, Ben Falk, Gerald Nepom

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

CD4+ T cells specific for the diabetes-associated autoantigen GAD65 were analyzed using peripheral blood samples after pancreas transplantation in subjects with T1D with clinical evidence of recurrent autoimmune diabetes. MHC class II tetramers facilitated the identification and cloning of antigen-specific autoreactive cells, which were found at several time points over a multiyear span, in spite of chronic immunosuppression of the subjects. Comparisons of TCR clonotypes by cDNA sequencing revealed that identical T cells were present in the circulation, separated by long time intervals, consistent with a persistent memory response associated with recurrent autoimmunity.

Original language	English (US)
Pages (from-to)	23-30
Number of pages	8
Journal	Clinical Immunology
Volume	128
Issue number	1
DOIs	https://doi.org/10.1016/j.clim.2008.03.459
State	Published - Jul 2008

Keywords

Autoimmune disease
CD4 T cells
GAD65
Islet replacement therapy
MHC class II tetramer
Pancreas transplantation
Type 1 diabetes

ASJC Scopus subject areas

Immunology
Immunology and Allergy

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title = "Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation",

abstract = "CD4+ T cells specific for the diabetes-associated autoantigen GAD65 were analyzed using peripheral blood samples after pancreas transplantation in subjects with T1D with clinical evidence of recurrent autoimmune diabetes. MHC class II tetramers facilitated the identification and cloning of antigen-specific autoreactive cells, which were found at several time points over a multiyear span, in spite of chronic immunosuppression of the subjects. Comparisons of TCR clonotypes by cDNA sequencing revealed that identical T cells were present in the circulation, separated by long time intervals, consistent with a persistent memory response associated with recurrent autoimmunity.",

keywords = "Autoimmune disease, CD4 T cells, GAD65, Islet replacement therapy, MHC class II tetramer, Pancreas transplantation, Type 1 diabetes",

author = "Elsa Laughlin and George Burke and Alberto Pugliese and Ben Falk and Gerald Nepom",

note = "Funding Information: This study was supported by grants from the National Institutes of Health (DK070011 and AI050864) and the Juvenile Diabetes Research Foundation. We thank Dr. Eddie James for tetramer production, Tuan Nguyen for technical assistance, and the clinical research team at the University of Miami pancreas transplant registry.",

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AU - Laughlin, Elsa

AU - Burke, George

AU - Pugliese, Alberto

AU - Falk, Ben

AU - Nepom, Gerald

N1 - Funding Information: This study was supported by grants from the National Institutes of Health (DK070011 and AI050864) and the Juvenile Diabetes Research Foundation. We thank Dr. Eddie James for tetramer production, Tuan Nguyen for technical assistance, and the clinical research team at the University of Miami pancreas transplant registry.

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AB - CD4+ T cells specific for the diabetes-associated autoantigen GAD65 were analyzed using peripheral blood samples after pancreas transplantation in subjects with T1D with clinical evidence of recurrent autoimmune diabetes. MHC class II tetramers facilitated the identification and cloning of antigen-specific autoreactive cells, which were found at several time points over a multiyear span, in spite of chronic immunosuppression of the subjects. Comparisons of TCR clonotypes by cDNA sequencing revealed that identical T cells were present in the circulation, separated by long time intervals, consistent with a persistent memory response associated with recurrent autoimmunity.

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