title: Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation.
abstract: Repetitive antigen stimulation by prime-boost vaccination or pathogen reencounter increases memory CD8(+) T cell numbers, but the impact on memory CD8(+) T cell differentiation is unknown. Here we showed that repetitive antigen stimulations induced accumulation of memory CD8(+) T cells with uniform effector memory characteristics. However, genome-wide microarray analyses revealed that each additional antigen challenge resulted in the differential regulation of several hundred new genes in the ensuing memory CD8(+) T cell populations and, therefore, in stepwise diversification of CD8(+) T cell transcriptomes. Thus, primary and repeatedly stimulated (secondary, tertiary, and quaternary) memory CD8(+) T cells differed substantially in their molecular signature while sharing expression of a small group of genes and biological pathways, which may constitute a core signature of memory differentiation. These results reveal the complex regulation of memory CD8(+) T cell differentiation and identify potential new molecular targets to dissect the function of memory cells generated by repeated antigen stimulation.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wirth
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Xue
authors.forename: Deepa
authors.initials: D
authors.lastname: Rai
authors.forename: Jaime T
authors.initials: JT
authors.lastname: Sabel
authors.forename: Tom
authors.initials: T
authors.lastname: Bair
authors.forename: John T
authors.initials: JT
authors.lastname: Harty
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Badovinac
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D000941:Antigens; D010047:Ovalbumin