Cytokine-dependent Blimp-1 expression in activated T cells inhibits IL-2 production.
After Ag activation of naive T cells in vitro, extensive growth and differentiation into effector cells depend upon IL-2. DNA microarray analysis was used to identify IL-2-dependent molecules regulating this process. In this study, we show that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is expressed by a cytokine-dependent pathway in activated T lymphocytes. IL-2 production by activated CD4(+) and CD8(+) T cells inversely correlated with Blimp-1 levels as higher IL-2 production was associated with lower Blimp-1 expression. Furthermore, ectopic expression of Blimp-1 by activated T cells inhibited IL-2 production but enhanced granzyme B and CD25 expression. Collectively, these findings indicate that there is a negative feedback regulatory loop in activated T cells such that IL-2 inhibits its own production through induction of Blimp-1 while promoting an effector cell phenotype.
Gong
Dapeng
D
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
Malek
Thomas R
TR
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053804:Granzymes / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053804:Granzymes; C509214:Gzmb protein, mouse