In vivo elimination of MHC-I-deficient lymphocytes by activated natural killer cells is independent of granzymes A and B
| Autor: | Arno Müllbacher, Lisa Pavlinovic, Nicolie Young, Matthias Regner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Cytotoxicity
Immunologic Tumor Immunology Immunology lcsh:Medicine NK cells Lymphocyte Activation Granzymes GZMB Mice Interleukin 21 MHC class I Animals Cytotoxic T cell Immunoassays Cytotoxicity lcsh:Science Biology Immune Response Multidisciplinary Lymphokine-activated killer cell biology Perforin Histocompatibility Antigens Class I Immune cells lcsh:R Immunity Immunologic Subspecialties Semliki forest virus Innate Immunity Cell biology Killer Cells Natural Mice Inbred C57BL Gene Expression Regulation Granzyme Immunologic Techniques biology.protein Female lcsh:Q Research Article |
| Zdroj: | PLoS ONE, Vol 6, Iss 8, p e23252 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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 β(2)microglobulin-deficient (MHC-I(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(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. |
| Databáze: | OpenAIRE |
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