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dc.contributor.authorChiang, Samuel C. C.
dc.contributor.authorTheorell, Jakob
dc.contributor.authorEntesarian, Miriam
dc.contributor.authorMeeths, Marie
dc.contributor.authorMastafa, Monika
dc.contributor.authorAl-Herz, Waleed
dc.contributor.authorFrisk, Per
dc.contributor.authorGilmour, Kimberly C.
dc.contributor.authorIfversen, Marianne
dc.contributor.authorLangenskiold, Cecilia
dc.contributor.authorMachaczka, Maciej
dc.contributor.authorNaqvi, Ahmed
dc.contributor.authorPayne, Jeanette
dc.contributor.authorPerez-Martinez, Antonio
dc.contributor.authorSabel, Magnus
dc.contributor.authorUnal, Ekrem
dc.contributor.authorUnal, Sule
dc.contributor.authorWiniarski, Jacek
dc.contributor.authorNordenskjold, Magnus
dc.contributor.authorLjunggren, Hans-Gustaf
dc.contributor.authorHenter, Jan-Inge
dc.contributor.authorBryceson, Yenan T.
dc.date.accessioned2019-12-10T10:35:22Z
dc.date.available2019-12-10T10:35:22Z
dc.date.issued2013
dc.identifier.issn0006-4971
dc.identifier.urihttps://doi.org/10.1182/blood-2012-07-442558
dc.identifier.urihttp://hdl.handle.net/11655/13869
dc.description.abstractCytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through the release of perforin-containing lytic granules. In the present study, we first performed probability-state modeling of differentiation and lytic granule markers on CD8(+) T cells to enable the comparison of bona fide CTLs with NK cells. Analysis identified CD57(bright) expression as a reliable phenotype of granule marker-containing CTLs. We then compared CD3(+)CD8(+)CD57(bright) CTLs with NK cells. Healthy adult peripheral blood CD3(+)CD8(+)CD57(bright) CTLs expressed more granzyme B but less perforin than CD3(-)CD56(dim) NK cells. On stimulation, such CTLs degranulated more readily than other T-cell subsets, but had a propensity to degranulate that was similar to NK cells. Remarkably, the CTLs produced cytokines more rapidly and with greater frequency than NK cells. In patients with biallelic mutations in UNC13D, STX11, or STXBP2 associated with familial hemophagocytic lymphohistiocytosis, CTL and NK cell degranulation were similarly impaired. Therefore, cytotoxic lymphocyte subsets have similar requirements for Munc13-4, syntaxin-11, and Munc18-2 in lytic granule exocytosis. The present results provide a detailed comparison of human CD3(+)CD8(+)CD57(bright) CTLs and NK cells and suggest that analysis of CD57(bright) CTL function may prove useful in the diagnosis of primary immunodeficiencies including familial hemophagocytic lymphohistiocytosis.
dc.language.isoen
dc.publisherAmer Soc Hematology
dc.relation.isversionof10.1182/blood-2012-07-442558
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHematology
dc.titleComparison Of Primary Human Cytotoxic T-Cell And Natural Killer Cell Responses Reveal Similar Molecular Requirements For Lytic Granule Exocytosis But Differences In Cytokine Production
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalBlood
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume121
dc.identifier.issue8
dc.identifier.startpage1345
dc.identifier.endpage1356
dc.description.indexWoS
dc.description.indexScopus


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