Recurrence of autoreactive antigen-specific CD4+ T cells in autoimmune diabetes after pancreas transplantation.
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.
Laughlin
Elsa
E
Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA 98101, USA.
Burke
George
G
Pugliese
Alberto
A
Falk
Ben
B
Nepom
Gerald
G
D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019070:Cell Lineage; D002999:Clone Cells; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000601:surgery*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control; D015804:HLA-DR4 Antigen; D006801:Humans; D016867:Immunocompromised Host; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016035:Pancreas Transplantation; D016032:Randomized Controlled Trials as Topic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2