Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2.
We demonstrate that interleukin-10 (IL-10) can inhibit T-cell apoptosis. T cells, within a PBMC (peripheral blood mononuclear cell) population, were stimulated via the T-cell receptor and grown in the presence of IL-2. These cells had less apoptosis when in the continuous presence of IL-10, compared with cells grown in the absence of IL-10. Conversely, when stimulated and grown in the presence of neutralizing antibody of IL-10, there was an increase in T-cell apoptosis. The in vitro rescue from apoptotic cell death of other lymphoid cells, such as germinal centre B cells, has been shown by others to involve a Bcl-2 pathway. We therefore investigated whether IL-10 might affect the Bcl-2 expression on cultured T cells. By Western blotting we demonstrated that continuous exposure of IL-10 to T cells (within a PBMC population) enhanced the expression of Bcl-2. Furthermore, T cells protected from apoptotic cell death by IL-10 were indistinguishable from viable untreated cells in their ability to proliferate to either immobilized anti-CD3 or IL-2. Thus, we have shown that continuous culture of T cells in the presence of IL-10 will inhibit T-cell apoptosis because of, at least in part, the upregulation of Bcl-2, and this is associated with a normal proliferative function.
Cohen
S B
SB
Mathilda and Terence Kennedy Institute of Rheumatology, UK.
Crawley
J B
JB
Kahan
M C
MC
Feldmann
M
M
Foxwell
B M
BM
D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D016753:Interleukin-10