CTL: virus control cells first and cytolytic cells second? DNA fragmentation, apoptosis and the prelytic halt hypothesis

Martz, Eric; Howell, Donna

doi:10.1016/0167-5699(89)90231-4

Cited by 155 publications

(44 citation statements)

References 57 publications

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“…In the latter case, whether the laddering is an endogenous property of the cell line or a response to a virally introduced gene is unclear. In fact, apoptosis has been suggested to have evolved as an antiviral defense (37). Consequently, apoptosis might be a phylogenetically newer cell death mechanism.…”

Section: Discussionmentioning

confidence: 99%

Do all programmed cell deaths occur via apoptosis?

Schwartz

Smith

Jones

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

506

242

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During development, large numbers of cells die by a nonpathological process referred to as programmed cell death. In many tissues, dying cells display similar changes in morphology and chromosomal DNA organization, which has been termed apoptosis. Apoptosis is such a widely documented phenomenon that many authors have assumed all programmed cell deaths occur by this process. Two well-characterized model systems for programmed cell death are (i) the death of T cells during negative selection in the mouse thymus and (ii) the loss of intersegmental muscles of the moth Manduca sexta at the end of metamorphosis. In this report we compare the patterns of cell death displayed by T cells and the intersegmental muscles and find that they differ in terms of cell-surface morphology, nuclear ultrastructure, DNA fragmentation, and polyubiquitin gene expression. Unlike the T cells, which are known to die via apoptosis, we find that the intersegmental muscles display few of the features that characterize apoptosis. These data suggest that more than one cell death mechanism is used during development.

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Section: Discussionmentioning

confidence: 99%

Do all programmed cell deaths occur via apoptosis?

Schwartz

Smith

Jones

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

506

242

View full text Add to dashboard Cite

show abstract

“…At least two, not necessarily exclusive, modes of action by which gzmA and gzmB mediate recovery from Ect infection can be envisaged. First, both gzms may facilitate induction of DNA damage and͞or DNA fragmentation (15)(16)(17)(18)(19)(20)(21)(22), a process that also may affect poxvirus double-stranded DNA stability (42). In fact, gzmB has been shown to facilitate induction of apoptosis via activation of caspases (43), thereby accelerating nucleolysis.…”

Section: Discussionmentioning

confidence: 99%

Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes

Müllbacher

Waring

Hla

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

195

174

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Analysis of perforin-deficient mice has identified the cytolytic pathway and perforin as the preeminent effector molecule in T cellmediated control of virus infections. In this paper, we show that mice lacking both granzyme A (gzmA) and granzyme B (gzmB), which are, beside perforin, key constituents of cytolytic vesicles, are as incapable as are perforin-deficient mice of controlling primary infections by the natural mouse pathogen ectromelia, a poxvirus. Death of gzmA؋gzmB double knockout mice occurred in a dose-dependent manner, despite the expression of functionally active perforin and the absence of an intrinsic defect to generate splenic cytolytic T cells. These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens.

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“…؉ C ytotoxic T lymphocytes play a key role in immune responses by directly killing target cells (TCs), 3 such as virus-infected cells, tumors, intracellular parasites, and allogeneic grafts, in an Ag-specific manner (1)(2)(3)(4)(5). However, naive immature CD8…”

Section: Cd4mentioning

confidence: 99%

CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation

Kojima

Kanno

Häse

et al. 2005

The Journal of Immunology

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This study was designed to determine the role of CD25+CD4+ regulatory T (Tr) cells in CTL maturation and effector functions using a murine CTL line and in vitro MLC. Tr cells inhibited CTL functional maturation, but had no effect on CTL effector functions. In CD4+ responder T cell-depleted MLC supplemented with IL-2, Tr cells suppressed mature CTL generation only when added within the first 2 days of culture. Tr cells down-regulated levels of active Akt, but not STAT5 or ZAP70 in Ag-primed immature CTLs. Down-regulation of active Akt was accompanied by a reduction in CTL cell size and IL-2Rα expression. In Tr cell-depleted MLC, CTLs were generated that exhibited high levels of nonspecific cytotoxicity. Our in vitro findings suggest that Tr cells regulate functional CTL maturation to generate optimal Ag-specific immune responses through the control of the PI3K/Akt pathway.

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CTL: virus control cells first and cytolytic cells second? DNA fragmentation, apoptosis and the prelytic halt hypothesis

Cited by 155 publications

References 57 publications

Do all programmed cell deaths occur via apoptosis?

Do all programmed cell deaths occur via apoptosis?

Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes

CD4+CD25+ Regulatory T Cells Attenuate the Phosphatidylinositol 3-Kinase/Akt Pathway in Antigen-Primed Immature CD8+ CTLs during Functional Maturation

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