Blimp-1 induced by IL-4 plays a critical role in suppressing IL-2 production in activated CD4 T cells.
Although an inhibitory function of IL-4 in CD4 T cell IL-2 production has long been recognized, a mechanism mediating the inhibition remains unclear. In this study we demonstrate that IL-4 displays a potent suppressive function in IL-2 production of activated CD4 T cells through STAT6. IL-4-induced IL-2 suppression required IL-2 because IL-2 neutralization restored the production of IL-2 even in the presence of IL-4. In vivo, enhanced IL-2 production was found in nematode-infected IL-4- or STAT6-deficient animals, whereas immunization in the presence of IL-4 substantially diminished IL-2 production by Ag-specific CD4 T cells. IL-2 mRNA expression was reduced when T cells were stimulated in the presence of IL-4, whereas IL-2 mRNA decay was unaltered, suggesting that IL-4 mediates the suppression at a transcriptional level. Blimp-1 induced by IL-4 stimulation in activated CD4 T cells was found to be necessary to mediate the IL-2 inhibition as IL-4-mediated IL-2 suppression was less pronounced in activated CD4 T cells deficient in Blimp-1. Taken together, our results demonstrate a potential link with IL-4, Blimp-1, and IL-2 production, suggesting that Blimp-1 may play an important role in controlling IL-2 production in activated T cells and in adaptive T cell immunity.
Wang
Lu
L
Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
van Panhuys
Nicholas
N
Hu-Li
Jane
J
Kim
Sohee
S
Le Gros
Graham
G
Min
Booki
B
D000818:Animals; D000947:Antigens, Helminth / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009559:Nippostrongylus / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017206:Strongylida Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000947:Antigens, Helminth; D007376:Interleukin-2; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D014157:Transcription Factors; D015847:Interleukin-4; D000074462:Positive Regulatory Domain I-Binding Factor 1