title: IL-2 induction of Blimp-1 is a key in vivo signal for CD8+ short-lived effector T cell differentiation.
abstract: During infection or vaccination, only a small proportion of CD8(+) T cells differentiate into memory cells. The mechanisms underlying the differentiation of CD8(+) T cells into short-lived effector cells (SLECs) or memory precursor effector cells are poorly defined. It was recently shown in infectious models that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) enhances the formation of SLECs. The factors controlling Blimp-1 expression leading to the in vivo formation of SLECs are still not known. However, it has been shown that cytokines such as IL-2 induce Blimp-1 expression in vitro. In this study, we took advantage of the low-inflammation model of dendritic cell immunization to study the role of the IL-2/Blimp-1 axis in SLEC differentiation as well as the importance of Blimp-1 expression in memory precursor effector cells for proper CD8(+) memory generation. Our results show that Blimp-1 deficiency affects effector differentiation and function in the absence of inflammation. Unexpectedly, memory generation was not affected in Blimp-1-deficient OT-I cells responding to vaccination. In addition, modulation of the bioavailability of IL-2 by injection either of a blocking Ab or of the cytokine, demonstrates a link between IL-2, Blimp-1 induction, and SLEC formation in wild-type cells. Conversely, injection of IL-2 had less effect on Blimp-1-deficient CD8(+) T cells, indicating that the effect of IL-2 on in vivo SLEC differentiation is mediated by Blimp-1. In conclusion, IL-2 induction of Blimp-1 expression is a key regulator of SLEC differentiation in vivo.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada;
authors.forename: Salix
authors.initials: S
authors.lastname: Boulet
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada;
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Daudelin
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada; Department of Medicine, University of Montreal, Montreal, Quebec H3C 3J7, Canada; and Department of Microbiology, Immunology and Infectiology, University of Montreal, Montreal, Quebec H3C 3J7, Canada nathalie.labrecque@umontreal.ca.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D037181:Lectins, C-Type; D008089:Listeria monocytogenes / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; D019496:Cancer Vaccines; D007376:Interleukin-2; D053699:Interleukin-7 Receptor alpha Subunit; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; C513258:Prdm1 protein, mouse; D011971:Receptors, Immunologic; D014157:Transcription Factors; D007371:Interferon-gamma; D010047:Ovalbumin; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053804:Granzymes; C509214:Gzmb protein, mouse