Interleukin-2 induces apoptosis in mouse thymocytes.
Interleukins play a role in the process of T-cell development and, like other cytokines, seem able to modulate apoptosis. Interleukin-2 has been reported to inhibit apoptotic cell death of thymocytes induced in vitro by either activation of CD3/TCR complex or treatment with glucocorticoid hormone. We demonstrate here that IL-2 can provoke DNA fragmentation and cell death of CD4+ CD8+ mouse thymocytes by activating an endogenous apoptotic pathway. Thymocytes, incubated with high IL-2 concentrations in vitro, showed the morphological characteristics of apoptotic cells, including reduction in nuclear size, derangement in chromatin structure, and DNA fragmentation in oligonucleosomal subunits. Inhibition of mRNA and protein synthesis and addition of the PKC-inhibitor H-7, Zn2+ ions, and IL-4 counteracted the IL-2 effect. These data suggest that high IL-2 concentrations may induce an active process of cell death on mouse thymocytes in vitro.
Migliorati
G
G
Istituto di Farmacologia Medica, Perugia University Medical School, Italy.
Nicoletti
I
I
Pagliacci
M C
MC
D'Adamio
L
L
Riccardi
C
C
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens; D016827:CD8 Antigens; D002478:Cells, Cultured / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D007546:Isoquinolines; D010879:Piperazines; D011994:Recombinant Proteins; D015847:Interleukin-4; D003907:Dexamethasone; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015032:Zinc