IL-2 protects T cell hybrids from the cytolytic effect of glucocorticoids. Synergistic effect of IL-2 and dexamethasone in the induction of high-affinity IL-2 receptors.
IL-2-independent CD8+ rat x BW5147 T cell hybridomas are highly sensitive to treatment with 10(-6) M dexamethasone. This glucocorticoid analog induces a rapid DNA fragmentation with a pattern similar to that observed during glucocorticoid-induced killing of mouse thymocytes, which suggests the activation of a similar specific endonuclease. Among these hybrids, we select variants expressing low affinity IL-2R, as measured by IL-2 binding assay and by the cell surface expression of the IL-2Rp55 Ag (rat CD25 recognized by OX-39 mAb). These OX-39+ IL-2 independent hybrids (named V type) are protected from the toxic action of dexamethasone by IL-2. The addition of IL-2 to V type cells induces the expression of a low number of high affinity IL-2R, which is strongly potentiated by the simultaneous addition of dexamethasone. Furthermore, dexamethasone is strongly synergistic with IL-2 in the induction of mRNA p55/IL-2R, which could be observed 6 h after the treatment. These data suggest that the utilization of the IL-2-R signaling pathway may induce an effective protection against glucocorticoid toxicity in mature T cells. Finally, we proved that the upregulation of IL-2R by IL-2 is strongly potentiated by glucocorticoids, which implies a new role for these agents in the immune system.
Fernández-Ruiz
E
E
Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Rebollo
A
A
Nieto
M A
MA
Sanz
E
E
Somoza
C
C
Ramirez
F
F
Lopez-Rivas
A
A
Silva
A
A
D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D004249:DNA Damage; D003907:Dexamethasone / Q000633:toxicity*; D004357:Drug Synergism; D005786:Gene Expression Regulation; D006822:Hybrid Cells / Q000187:drug effects* / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003907:Dexamethasone