Relationship between HLA genotype and the functional profile of Ag-specific CD8 T-cells : 39
Details
Serval ID
serval:BIB_743DD45FA7E0
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Relationship between HLA genotype and the functional profile of Ag-specific CD8 T-cells : 39
Title of the conference
Annual Joint Meeting of the Swiss Societies for Pneumology, Paediatric Pneumology, Allergology and Immunology, Thoracic Surgery
Address
Fribourg, April 17 and 18, 2008
ISBN
1424-7860
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
138
Series
Swiss Medical Weekly
Pages
47S
Language
english
Notes
Background: Degranulation activity, as measured by CD107a mobilization, is commonly used to define cytotoxic CD8 T-cells.
However, the relationship between granule's content and cytotoxic capacity of virus-specific CD8 T-cells was never investigated.
Methods: A variety of virus-specific CD8 T-cell responses including CMV (n = 16), EBV (n = 21) and Flu (n = 17) were identified using tetramer complexes or peptide stimulation and analyzed for CD107a mobilization, as well as for the simultaneous expression of perforin (Perf), granzyme (Grz) A, GrzB and GrzK by polychromatic flow cytometry combined with CD127 (i.e. IL-7Ra), CCR7 and CD45RA, that were used to assess T-cell differentiation. Results: Polychromatic flow cytometric analyses combining GrzA, GrzB, GrzK and Perf on CD8 T-cells identified 16 distinct populations. Highly differentiated cells (CCR7-CD127-CD45RA±) mostly contained Perf and GrzB, but not GrzA or GrzK, which in contrast were mostly found in poorly differentiated CD8 T-cells (CCR7+CD127+CD45RA-). Interestingly, analysis of the different viruses showed typical virusspecific
patterns. CMV-specific T-cells were mostly composed of four distinct subsets and >35% of cell were Perf+GrzB+GrzA+GrzK±.
Three distinct subsets were observed in EBV-specific T-cells and >40% of cell were Perf-GrzK+GrzB±GrzA±. Whereas above 60% of Flu-specific T-cells were Perf-GrzK+GrzB-GrzA-. Differences between the viruses were highly significant (All P <0.01). Of note, Flu-specific CD8 T cells, i.e. lacking perf and GrzB, did not show direct ex vivo cytotoxicity despite the fact that a similar level of degranulation activity was observed in Flu-, EBV- and CMV-specific CD8 T cells (ranging from 40-60%, P >0.05) following stimulation with the same peptides.
Conclusions: The composition of granules is highly heterogeneous in CD8 T-cells and associated with differentiation. However, typical patterns of granule's content are observed for the different viruses and lack of perforin is associated with the absence of cytotoxic activity. In contrast, degranulation activity is consistently observed in all models of virus infection (including non cytotoxic responses) and therefore represents an irrelevant marker of CD8 T-cells with cytotoxic capacity.
However, the relationship between granule's content and cytotoxic capacity of virus-specific CD8 T-cells was never investigated.
Methods: A variety of virus-specific CD8 T-cell responses including CMV (n = 16), EBV (n = 21) and Flu (n = 17) were identified using tetramer complexes or peptide stimulation and analyzed for CD107a mobilization, as well as for the simultaneous expression of perforin (Perf), granzyme (Grz) A, GrzB and GrzK by polychromatic flow cytometry combined with CD127 (i.e. IL-7Ra), CCR7 and CD45RA, that were used to assess T-cell differentiation. Results: Polychromatic flow cytometric analyses combining GrzA, GrzB, GrzK and Perf on CD8 T-cells identified 16 distinct populations. Highly differentiated cells (CCR7-CD127-CD45RA±) mostly contained Perf and GrzB, but not GrzA or GrzK, which in contrast were mostly found in poorly differentiated CD8 T-cells (CCR7+CD127+CD45RA-). Interestingly, analysis of the different viruses showed typical virusspecific
patterns. CMV-specific T-cells were mostly composed of four distinct subsets and >35% of cell were Perf+GrzB+GrzA+GrzK±.
Three distinct subsets were observed in EBV-specific T-cells and >40% of cell were Perf-GrzK+GrzB±GrzA±. Whereas above 60% of Flu-specific T-cells were Perf-GrzK+GrzB-GrzA-. Differences between the viruses were highly significant (All P <0.01). Of note, Flu-specific CD8 T cells, i.e. lacking perf and GrzB, did not show direct ex vivo cytotoxicity despite the fact that a similar level of degranulation activity was observed in Flu-, EBV- and CMV-specific CD8 T cells (ranging from 40-60%, P >0.05) following stimulation with the same peptides.
Conclusions: The composition of granules is highly heterogeneous in CD8 T-cells and associated with differentiation. However, typical patterns of granule's content are observed for the different viruses and lack of perforin is associated with the absence of cytotoxic activity. In contrast, degranulation activity is consistently observed in all models of virus infection (including non cytotoxic responses) and therefore represents an irrelevant marker of CD8 T-cells with cytotoxic capacity.
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Create date
13/10/2009 14:17
Last modification date
20/08/2019 15:32
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