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In vivo elimination of MHC-I-deficient lymphocytes by activated natural killer cells is independent of granzymes A and B.

NK cells kill target cells mainly via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and induction of apoptosis is severely impaired in the absence of gzm A and B. However, their importance for in vivo... Full description

Journal Title: PloS one 2011, Vol.6(8), p.e23252
Main Author: Regner, Matthias
Other Authors: Pavlinovic, Lisa , Young, Nicolie , Müllbacher, Arno
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0023252
Link: http://search.proquest.com/docview/884426282/?pq-origsite=primo
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title: In vivo elimination of MHC-I-deficient lymphocytes by activated natural killer cells is independent of granzymes A and B.
format: Article
creator:
  • Regner, Matthias
  • Pavlinovic, Lisa
  • Young, Nicolie
  • Müllbacher, Arno
subjects:
  • Animals–Genetics
  • Cytotoxicity, Immunologic–Deficiency
  • Female–Metabolism
  • Gene Expression Regulation–Immunology
  • Granzymes–Immunology
  • Histocompatibility Antigens Class I–Virology
  • Killer Cells, Natural–Immunology
  • Lymphocyte Activation–Metabolism
  • Mice–Physiology
  • Mice, Inbred C57bl–Physiology
  • Perforin–Physiology
  • Semliki Forest Virus–Physiology
  • Histocompatibility Antigens Class I
  • Perforin
  • Granzymes
ispartof: PloS one, 2011, Vol.6(8), p.e23252
description: NK cells kill target cells mainly via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and induction of apoptosis is severely impaired in the absence of gzm A and B. However, their importance for in vivo cytotoxicity by cytotoxic T cells has been questioned. We used an in vivo NK cytotoxicity assay, in which splenocytes from wild-type and [beta].sub.2 microglobulin-deficient (MHC-I.sup.neg) mice are co-injected into recipients whose NK cells were activated by virus infection or synthetic Toll-like receptor ligands. Elimination of adoptively transferred MHC-I.sup.neg splenocytes was unimpaired in the absence of gzmA and gzmB, but dependent on perforin. This target cell rejection was NK cell dependent, since NK cell depletion abrogated it. Furthermore, target cell elimination in vivo was equally rapid in both wild-type and gzmAxB-deficient recipients, with the majority of specific target cells lost from lymphoid tissue within less than one to two hours after transfer. Thus, similar to T cell cytotoxicity, the contribution of gzmA and B to in vivo target cell elimination remains unresolved.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0023252
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleIn vivo elimination of MHC-I-deficient lymphocytes by activated natural killer cells is independent of granzymes A and B.
creatorRegner, Matthias ; Pavlinovic, Lisa ; Young, Nicolie ; Müllbacher, Arno
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identifierE-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0023252
subjectAnimals–Genetics ; Cytotoxicity, Immunologic–Deficiency ; Female–Metabolism ; Gene Expression Regulation–Immunology ; Granzymes–Immunology ; Histocompatibility Antigens Class I–Virology ; Killer Cells, Natural–Immunology ; Lymphocyte Activation–Metabolism ; Mice–Physiology ; Mice, Inbred C57bl–Physiology ; Perforin–Physiology ; Semliki Forest Virus–Physiology ; Histocompatibility Antigens Class I ; Perforin ; Granzymes
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descriptionNK cells kill target cells mainly via exocytosis of granules containing perforin (perf) and granzymes (gzm). In vitro, gzm delivery into the target cell cytosol results in apoptosis, and induction of apoptosis is severely impaired in the absence of gzm A and B. However, their importance for in vivo cytotoxicity by cytotoxic T cells has been questioned. We used an in vivo NK cytotoxicity assay, in which splenocytes from wild-type and [beta].sub.2 microglobulin-deficient (MHC-I.sup.neg) mice are co-injected into recipients whose NK cells were activated by virus infection or synthetic Toll-like receptor ligands. Elimination of adoptively transferred MHC-I.sup.neg splenocytes was unimpaired in the absence of gzmA and gzmB, but dependent on perforin. This target cell rejection was NK cell dependent, since NK cell depletion abrogated it. Furthermore, target cell elimination in vivo was equally rapid in both wild-type and gzmAxB-deficient recipients, with the majority of specific target cells lost from lymphoid tissue within less than one to two hours after transfer. Thus, similar to T cell cytotoxicity, the contribution of gzmA and B to in vivo target cell elimination remains unresolved.
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