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The Journal of Immunology, Vol 131, Issue 2 701-705, Copyright © 1983 by American Association of Immunologists

ARTICLES

The human immune response to insulin. I. Kinetic and cellular aspects of lymphocyte proliferative responses in diabetics

LJ Nell and JW Thomas

A reproducible culture system was developed with the use of peripheral blood mononuclear cells (MNC) from insulin-dependent diabetic subjects to assay T cell proliferation in response to mammalian insulins. Kinetic analysis revealed that maximal responses occur after 8 to 10 days of culture with 50 to 100 micrograms of insulin. Characterization of the cells involved showed that two cell types are required for this proliferative response: a radioresistant non-T cell and an E rosette- forming (T) lymphocyte. With the use of this assay, 16 of 32 insulin- dependent diabetics had demonstrable MNC proliferation in response to insulin or to the control antigen, tetanus toxoid. Among those 16 subjects a spectrum of responsiveness to insulin was found. Because MNC from all responsive subjects react to both beef and pork insulin, it appears that shared determinants are recognized by insulin-immune lymphocytes in this outbred population. In addition, cells from one subject were found to respond in a determinant-specific manner to the A- chain loop of beef insulin. Reproducibility of the assay was demonstrated over an 8-mo period in three experiments with the use of MNC from a single subject. This reliable assay of T lymphocyte responses to a defined antigen will help determine the fine specificity and genetic regulation of the immune response to insulin in man.


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S. E. Fineberg, T. T. Kawabata, D. Finco-Kent, R. J. Fountaine, G. L. Finch, and A. S. Krasner
Immunological Responses to Exogenous Insulin
Endocr. Rev., October 1, 2007; 28(6): 625 - 652.
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