title: Phenotypic CD8+ T cell diversification occurs before, during, and after the first T cell division.
abstract: Effector T cell responses rely on a phenotypically and functionally heterogeneous population of cells. Whether this diversity is programmed before clonal expansion or in later phases as a result of stochastic events or asymmetric cell division is not fully understood. In this study, we first took advantage of a sensitive in vitro assay to analyze the composition of single CD8(+) T cell progenies. Heterogeneity was predominantly observed between progenies of distinct clones, but could also be detected within individual progenies. Furthermore, by physically isolating daughter cells of the first T cell division, we showed that differences in paired daughter cell progenies contributed to intraclonal diversification. Finally, we developed an in vivo limiting dilution assay to compare individual T cell progenies following immunization. We provided evidence for simultaneous intraclonal and interclonal diversification in vivo. Our results support the idea that T cell diversification is a continuous process, initiated before clonal expansion and amplified during the first and subsequent cell divisions.
authors.affiliation: Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaître
authors.forename: Hélène D
authors.initials: HD
authors.lastname: Moreau
authors.forename: Laura
authors.initials: L
authors.lastname: Vedele
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D019070:Cell Lineage; D060966:Clonal Selection, Antigen-Mediated / Q000276:immunology; D002999:Clone Cells / Q000166:cytology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D016130:Immunophenotyping / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D019041:L-Selectin / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D053645:Interleukin-2 Receptor alpha Subunit; C110366:OVA-8; D010446:Peptide Fragments; D019041:L-Selectin; D010047:Ovalbumin