Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.
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.
Naquet
P
P
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Ellis
J
J
Kenshole
A
A
Semple
J W
JW
Delovitch
T L
TL
D000328:Adult; D000906:Antibodies / Q000032:analysis; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance / Q000276:immunology*; D013431:Sulfates / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000906:Antibodies; D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007328:Insulin; D013431:Sulfates