Interleukin-15 differentially enhances the expression of interferon-gamma and interleukin-4 in activated human (CD4+) T lymphocytes.
In this study interleukin (IL)-15 was examined for its ability to modulate the expression of interferon-gamma (IFN-gamma) and IL-4 in activated human T lymphocytes. The effect of IL-15 was compared with IL-2 and IL-7, cytokines all known to use the IL-2 receptor gammaC chain. The results demonstrate that the extent of upregulation of IFN-gamma and IL-4 mRNA was dependent on the applied cytokine (IL-2>IL-15>IL-7) and on the stimulatory signal. IFN-gamma and IL-4 mRNAs were upregulated by IL-15 in concanavalin A- (twofold) and anti-CD3 plus anti-CD28- (fivefold) stimulated T lymphocytes. IFN-gamma mRNA accumulation, but not IL-4 mRNA, was additively upregulated by IL-15 plus IL-7 (ninefold) in anti-CD3 stimulated T lymphocytes, and bypassed the requirement of CD28 signalling. Fluorescence-activated cell sorting (FACS) experiments demonstrated that IFN-gamma mRNA was upregulated by IL-15 in both CD4+ and CD8+ T lymphocytes, whereas IL-4 mRNA accumulation predominantly occurred in CD4+ cells. Preincubation of highly purified CD4+ T lymphocytes during 7 days with IL-15 and/or IL-7, followed by activation, also showed enhanced IL-4 protein secretion, but predominantly upregulated IFN-gamma protein. The net effect was a dramatically increased IFN-gamma/IL-4 ratio. Taken together, IL-15 and IL-7 can act as costimulatory signals, which may favour a T helper 1 (Th1) immune response, particularly in the absence of sufficient CD28 costimulation.
Borger
P
P
Divisions of Allergology, Hematology, and Pulmonology, Department of Medicine, University of Groningen, The Netherlands.
Kauffman
H F
HF
Postma
D S
DS
Esselink
M T
MT
Vellenga
E
E
D000906:Antibodies / Q000494:pharmacology; D015152:Blotting, Northern; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics*; D019409:Interleukin-15 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D019409:Interleukin-15; D012333:RNA, Messenger; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma