Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients (original) (raw)

Summary

The bcl-2 gene product has been shown to regulate apoptotic cell death, and its dysregulation has been shown to induce several abnormalities in the immune system. No data exist regarding bcl-2 expression in autoimmune diseases, such as human insulin-dependent diabetes mellitus (IDDM). We investigated bcl-2 protein expression by testing T lymphocytes from 15 newly-diagnosed (<3 weeks) IDDM patients in comparison to 10 age-matched control subjects. The expression of bcl-2 on CD3+ lymphocyte subsets was investigated after membrane permeabilization by two- or three-colour immunofluorescence. When the percentage and mean fluorescence intensity (MFI) of bcl-2+/CD3+ cells from normal individuals and patients were compared, we found that bcl-2 expression within the CD3+ and CD4+ CD45R0+ T-cell populations was reduced significantly in IDDM patients (46.8±15.4 vs 79.6±11.7; 25.7±3.8 vs 47.15±5.7, respectively; p<0.001). To establish whether low bcl-2 expression in T cells from newly-diagnosed patients reflects their susceptibility to death by an apoptotic process, we also evaluated DNA staining with propidium iodide in CD3+ lymphocyte suspension after a (24–72 h) culture period (spontaneous apoptosis). We found that IDDM patients have higher levels of spontaneous apoptosis (mean±SEM: 24 h=4.6±0.8; 48 h=9.9±1; 72 h=12.8±1.1) than control subjects (24 h=1.8±0.4; 48 h=4.6±0.4; 72 h=5.7±0.3; p<0.02–0.001). Our study suggests that recent onset IDDM is characterised by reduced bcl-2 expression, which in turn may be associated with the increased spontaneous apoptosis we observed.

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Abbreviations

MFI:

Mean fluorescence intensity

mAb:

monoclonal antibody

PMA:

phorbol myristate

PHA:

phytoemagglutinin

Con A:

concanavalin-A

PKC:

protein kinase C

ICA:

islet cell autoantibody

IAA:

insulin autoantibody

PE:

phycoerythrin

PI:

propidium iodide

FSC:

forward scatter

SSC:

side scatter

PBMC:

peripheral blood mononuclear cells

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Authors and Affiliations

  1. Laboratory of Immunology, Endocrinology Section, Institute of Clinica Medica, University of Palermo, Italy
    C. Giordano, G. Stassi, M. Todaro, R. De Maria, P. Richiusa, A. Scorsone, M. Giordano & A. Galluzzo

Authors

  1. C. Giordano
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  2. G. Stassi
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  3. M. Todaro
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  4. R. De Maria
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  5. P. Richiusa
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  6. A. Scorsone
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  7. M. Giordano
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  8. A. Galluzzo
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Giordano, C., Stassi, G., Todaro, M. et al. Low bcl-2 expression and increased spontaneous apoptosis in T-lymphocytes from newly-diagnosed IDDM patients.Diabetologia 38, 953–958 (1995). https://doi.org/10.1007/BF00400585

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