Cytotoxic T Lymphocytes: Target Cell Killing: Cellular Parameters

2007 ◽  
pp. 71-93
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Cell Killing

scholarly journals Studying the biology of cytotoxic T lymphocytes in vivo with a fluorescent granzyme B-mTFP knock-in mouse

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Praneeth Chitirala ◽  
Hsin-Fang Chang ◽  
Paloma Martzloff ◽  
Christiane Harenberg ◽  
Keerthana Ravichandran ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Fusion Protein ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Cell Function ◽  
Granzyme B ◽  
Cell Killing ◽  
Mouse Line

Understanding T cell function in vivo is of key importance for basic and translational immunology alike. To study T cells in vivo, we developed a new knock-in mouse line, which expresses a fusion protein of granzyme B, a key component of cytotoxic granules involved in T cell-mediated target cell-killing, and monomeric teal fluorescent protein from the endogenous Gzmb locus. Homozygous knock-ins, which are viable and fertile, have cytotoxic T lymphocytes with endogeneously fluorescent cytotoxic granules but wild-type-like killing capacity. Expression of the fluorescent fusion protein allows quantitative analyses of cytotoxic granule maturation, transport and fusion in vitro with super-resolution imaging techniques, and two-photon microscopy in living knock-ins enables the visualization of tissue rejection through individual target cell-killing events in vivo. Thus, the new mouse line is an ideal tool to study cytotoxic T lymphocyte biology and to optimize personalized immunotherapy in cancer treatment.

Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms

1994 ◽  
Vol 14 (1) ◽  
pp. 427-436
Author(s):  
D S Ucker ◽  
J D Wilson ◽  
L D Hebshi
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Active Cell ◽  
Death Process ◽  
Target Cells ◽  
Antigenic Stimulus ◽  
Cell Suicide

The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes to the target the single role of providing an antigenic stimulus to the CTL; this signal results in the vectoral degranulation and secretion of pore-forming elements onto the target. On the other hand, by a number of criteria, target cell death triggered by CTL appears fundamentally different from death resulting from membrane damage and osmotic lysis. CTL-triggered target cell death involves primary internal lesions of the target cell that reflect a physiological cell death process. Orderly nuclear disintegration, including lamin phosphorylation and solubilization, chromatin condensation, and genome digestion, are among the earliest events, preceding the loss of plasma membrane integrity. We have tested directly the involvement of the target cell in its own death by examining whether we could isolate mutants of target cells that have retained the ability to be recognized by and provide an antigenic stimulus to CTL while having lost the capacity to respond by dying. Here, we describe one such mutant, BW87. We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered target cell death under a variety of conditions. The identification of a mutable target cell element essential for the cell death response to CTL provides genetic evidence that target cell death reflects an active cell suicide process similar to other physiological cell deaths.

scholarly journals Serine esterase and hemolytic activity in human cloned cytotoxic T lymphocytes.

1988 ◽  
Vol 167 (2) ◽  
pp. 528-540 ◽  
Author(s):  
W S Ferguson ◽  
C R Verret ◽  
E B Reilly ◽  
M J Iannini ◽  
H N Eisen
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Hemolytic Activity ◽  
Active Sites ◽  
Blot Hybridization ◽  
Target Cells ◽  
Serine Esterase ◽  
Dot Blot ◽  
Ph Optimum

Target cell lysis by most murine cytotoxic T lymphocytes appears to be mediated by a complement (C9)-like protein called perforin, contained in high-density cytoplasmic granules. These granules also contain high levels of serine esterase activity, which may also play a role in cytolysis. Analysis of 17 cloned human cytotoxic T lymphocytes revealed the presence of serine esterase that is very similar to its murine counterpart in substrate and inhibitor specificities, pH optimum, and molecular mass; dot blot hybridization with synthetic oligonucleotides corresponding to the active sites of two known murine CTL esterases suggests homology to the murine enzyme HF. However, serine esterase was present at only approximately 10% of the level found in murine CTLs, and was not secreted during CTL-target cell interaction; moreover, hemolytic activity could not be detected in any of the seven cell lines tested. The results suggest that the human CTLs examined here kill their target cells by a mechanism different from that used by most cloned murine CTLs.

Killing Mechanisms of Cytotoxic T Lymphocytes

Physiology ◽  
1998 ◽  
Vol 13 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Peter Groscurth ◽  
Luis Filgueira
Keyword(s):  
T Lymphocytes ◽  
Ligand Binding ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Target Cells ◽  
Receptor Ligand

Cytotoxic T lymphocytes mediate lysis of target cells by various mechanisms, including exocytosis of lytic proteins (perforin, granzymes) and receptor-ligand binding of Fas/APO molecules. Death of target cells is characterized by either necrosis or apoptosis, depending on the killing mechanism used and on the metabolism of the target cell itself.

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