Differential role for IL-2 and IL-15 in the inhibition of apoptosis in short-term activated human lymphocytes.
Interleukin (IL)-15 is a newly described cytokine with properties similar to IL-2. Even though it does not share sequence homology with IL-2, both cytokines bind to the same receptor with the noted exception of a cytokine specific alpha-chain. In this study the authors compared IL-2 and IL-15 to determine their ability to rescue short term activated lymphocytes (phytohaemagglutinin stimulation of peripheral blood mononuclear cells for 6 days, followed by expansion in medium containing IL-2 for 2 days) from apoptotic cell death. The authors found that both IL-2 and IL-15 can inhibit induction of apoptosis in this experimental model with similar time and dose kinetics. On mRNA or protein levels induction of pro- and anti-apoptotic gene products like fasL, bcl-2, or bax with minor effects on fas/Apo-1 or bcl-XL was observed under culture conditions with both IL-2 and IL-15. Next, it was found that phytohaemagglutinin (PHA) blasts were less responsive (in terms of cellular proliferation and prevention from apoptosis) to IL-2 if signals through the alpha-chain were blocked, with no effect on beta-chain specific monoclonal antibodies (MoAb). By contrast, IL-15 was less effective in induction of cellular proliferation and prevention of apoptosis if IL-2R beta-chain specific MoAb were added to cell cultures. Testing intracellular signalling induced by IL-2 or IL-15, the authors found identical changes in tyrosine phosphorylation patterns in PHA blasts cultured in medium or under IL-2 or IL-15 stimulation. By contrast, they found consistent differences if PHA stimulated peripheral blood mononuclear cells (PBMC) were expanded in medium containing IL-15 (instead of IL-2). These IL-15 expanded PHA blasts showed a significantly increased percentage of apoptosis after growth factor withdrawal. Furthermore, IL-2 was more efficient than IL-15 in rescuing IL-15 expanded PHA blasts from apoptosis. In IL-15 expanded PHA blasts expression of IL-2R alpha-chain was lower than that in IL-2 expanded PHA blasts. A model presenting a differential role for IL-2 and IL-15 in inhibition of apoptosis in vivo is discussed.
Lorenz
H M
HM
Department of Medicine III, University of Erlangen-Nuremberg, Germany.
Hieronymus
T
T
Grünke
M
M
Manger
B
B
Kalden
J R
JR
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D010835:Phytohemagglutinins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors
D019409:Interleukin-15; D007376:Interleukin-2; D010835:Phytohemagglutinins