Interleukin-4 protects double-negative and CD4 single-positive thymocytes from dexamethasone-induced apoptosis.
Glucocorticoid hormones (GCH) and anti-CD3 monoclonal antibodies (MoAbs) induce in mouse thymocytes and T-cell tumor lines an active process of cell death called apoptosis. Interleukins (IL), including IL-1 and IL-2, have been reported to inhibit such apoptosis. In this study we show that IL-4 also reduced the DNA fragmentation characteristic of dexamethasone (DEX)-induced apoptosis in thymocytes. This effect, studied in both time-course and dose-response experiments, was also detected at low IL-4 concentrations (1 U/mL) and against high DEX levels (10(-7) mol/L). The effect of IL-4 was blocked by an anti-IL-4 but not by an anti-IL-1 alpha MoAb, and was thus both specific and direct. Phenotypic analysis showed that IL-4 protects predominantly CD4-CD8- and CD4+CD8- cells. Our findings suggest that intrathymic T-cell development may be influenced by IL-4.
Migliorati
G
G
Instituto di Farmacologia Medica, Perugia University Medical School, Italy.
Nicoletti
I
I
Pagliacci
M C
MC
D'Adamio
L
L
Riccardi
C
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D007375:Interleukin-1; D015847:Interleukin-4; D003907:Dexamethasone