Relationship between HLA genotype and the functional profile of Ag-specific CD8 T-cells : 39
Détails
ID Serval
serval:BIB_743DD45FA7E0
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
Relationship between HLA genotype and the functional profile of Ag-specific CD8 T-cells : 39
Titre de la conférence
Annual Joint Meeting of the Swiss Societies for Pneumology, Paediatric Pneumology, Allergology and Immunology, Thoracic Surgery
Adresse
Fribourg, April 17 and 18, 2008
ISBN
1424-7860
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
138
Série
Swiss Medical Weekly
Pages
47S
Langue
anglais
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.
Web of science
Création de la notice
13/10/2009 13:17
Dernière modification de la notice
20/08/2019 14:32
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