Interferon responsiveness of natural killer cells in type I human diabetes.
Abnormally low circulating numbers and function of NK cells are associated with new onset type I diabetes. Since alpha interferon is a stimulator of NK function, enriched T and non-T lymphocytes were incubated with 0, 100 and 1,000 units/ml of recombinant alpha interferon (rIFN alpha) and natural killing against K562 and pancreatic islet cell targets was measured. The killing of K562 (1:20 target:effector ratio) cells by non-T cells incubated with 0, 100 and 1,000 units/ml of rIFN alpha in patients was decreased to 27% (p less than 0.014 vs control), 34% (p less than 0.001) and 39% (p less than 0.003) when compared to killing by normal control non-T cells (48%, 74% and 58% respectively). T cell mediated killing of K562 cells in patients was decreased to 3.9% (p less than 0.03), 5.3% and 6.6% (p less than 0.003) when compared to that of controls (8.7%, 10-8% and 22.6% respectively). Non-T cell mediated killing of islet cells (1:20 target:effector ratio) following treatment of effector cells with 0, 100 and 1,000 units/ml of rIFN alpha in patients was 19%, 27%, and 26% which was comparable to control subjects killing of 31%, 18% and 37% respectively. Similar data were obtained using T-cells as effectors. These data indicate that in new onset type I diabetes; (a) NK cell functional activity is diminished in both T and non-T lymphocyte subpopulations and (b) NK activity is suboptimally enhanced with rIFN alpha.
Negishi
K
K
Department of Medicine, University of California, Irvine 92717.
Gupta
S
S
Chandy
K G
KG
Waldeck
N
N
Kershnar
A
A
Buckingham
B
B
Charles
M A
MA
D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002648:Child; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology* / Q000494:pharmacology; D012016:Reference Values
D007370:Interferon Type I; D011994:Recombinant Proteins