Dominant human CD8 T cell clonotypes persist simultaneously as memory and effector cells in memory phase.

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State: Public
Version: Final published version
Serval ID
serval:BIB_D53CB51E794F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dominant human CD8 T cell clonotypes persist simultaneously as memory and effector cells in memory phase.
Journal
Journal of Immunology
Author(s)
Touvrey C., Derré L., Devevre E., Corthesy P., Romero P., Rufer N., Speiser D.E.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
182
Number
11
Pages
6718-6726
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The adaptive immune system plays a critical role in protection at the time of secondary infection. It does so through the rapid and robust reactivation of memory T cells which are maintained long-term, in a phenotypically heterogeneous state, following their primary encounter with Ag. Although most HLA-A*0201/influenza matrix protein(58-66)-specific CD8 T cells from healthy donors display characteristics typical of memory T cells, through our extensive phenotypic analysis we have further shown that up to 20% of these cells express neither the IL-7 receptor CD127 nor the costimulatory molecule CD28. In contrast to the majority of CD28(pos) cells, granzyme B and perforin were frequently expressed by the CD28(neg) cells, suggesting that they are effector cells. Indeed, these cells were able to kill target cells, in an Ag-specific manner, directly ex vivo. Thus, our findings demonstrate the remarkable long-term persistence in healthy humans of not only influenza-specific memory cells, but also of effector T cells. We further observed that granzyme B expression in influenza-specific CD8 T cells paralleled levels in the total CD8 T cell population, suggestive of Ag-nonspecific bystander activation. Sequencing of TCR alpha- and beta-chains showed that the TCR repertoire specific for this epitope was dominated by one, or a few, T cell clonotype per healthy donor. Moreover, our sequencing analysis revealed, for the first time in humans, that identical clonotypes can coexist as both memory and effector T cells, thereby supporting the principle of multipotent clonotypic differentiation.
Keywords
Antigens, CD28/analysis, CD8-Positive T-Lymphocytes/immunology, Cell Differentiation, Clone Cells/immunology, Cytotoxicity, Immunologic, Granzymes/analysis, Humans, Immunologic Memory, Immunophenotyping, Interleukin-7 Receptor alpha Subunit/analysis, Perforin/analysis
Pubmed
Web of science
Open Access
Yes
Create date
08/10/2009 13:50
Last modification date
20/08/2019 16:55
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