Phenotypic CD8+ T Cell Diversification Occurs before, during, and after the First T Cell Division

• DOI: 10.4049/jimmunol.1300424
• Publication Date: 2013-07-09T02:52:40Z
• Authors: Fabrice Lemaître; Hélène D Moreau; Laura Vedele; Philippe Bousso
• Keywords: 0303 health sciences; [SDV.IMM] Life Sciences [q-bio]/Immunology; Ovalbumin; [SDV]Life Sciences [q-bio]; Interleukin-2 Receptor alpha Subunit; Epitopes, T-Lymphocyte; Dendritic Cells; CD8-Positive T-Lymphocytes; Flow Cytometry; Adoptive Transfer; Peptide Fragments; Clone Cells; Immunophenotyping; [SDV] Life Sciences [q-bio]; Mice, Inbred C57BL; Mice; 03 medical and health sciences; T-Lymphocyte Subsets; [SDV.IMM]Life Sciences [q-bio]/Immunology; Animals; Cell Lineage; L-Selectin; Clonal Selection, Antigen-Mediated; 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.