The in vitro responses of T cells from 13 insulin-nonresistant and 1 immunologically insulin-resistant (IIR) type I diabetes patients to sulfated beef insulin (SBI) were analyzed. Insulin A-loop specific CD4+ T cells from these patients did not respond to SBI. After 1 yr of treatment with SBI the IIR patient's T cell and antibody responses to beef, pork, and human insulin progressed from very high to nondetectable levels. This occurred in parallel to the appearance of her insulin-specific CD8+ T cells, which inhibited the response of her A-loop-specific CD4+ T cells to insulin. A transient increase in her CD8+ anti-insulin antibody activity coincided with a relative lack of her CD8+ T cell activity. CD8+ T cells that regulate T cell responsiveness to insulin are probably present but difficult to detect in most type I diabetes patients. These T cells were identified in only 2 of 13 insulin-nonresistant patients who presented with lipoatrophy and insulin allergy, respectively, and who possessed high-titered, anti-insulin antibodies. Our data demonstrate that CD8+ T cells play an important role in controlling peripheral tolerance to insulin and may abrogate IIR in a diabetic patient treated with SBI.
P Naquet, J Ellis, A Kenshole, J W Semple, T L Delovitch
Title and authors | Publication | Year |
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Hypoglycemia and Hyperglycemia Due to Insulin Antibodies against Therapeutic Human Insulin: Treatment with Double Filtration Plasmapheresis and Prednisolone
R Koyama, K Nakanishi, M Kato, S Yamashita, H Kuwahara, H Katori |
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Use of a Liposome Antigen Delivery System to Alter Immune Responses in Vivo
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Journal of Pharmaceutical Sciences | 1998 |
INSULINS
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Endocrinology & Metabolism Clinics of North America | 1997 |
Altered processing of human insulin by B lymphocytes from an immunologically insulinresistant type I diabetic patient
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Journal of Autoimmunity | 1991 |
Insulin-dependent (type I) diabetes mellitus
W Rodger |
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne | 1991 |