Perforin: structure and function

Liu, Chau‐Ching; Walsh, Craig M.; Young, John Ding‐E

doi:10.1016/0167-5699(95)80121-9

Cited by 321 publications

(201 citation statements)

References 80 publications

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“…A recent report that CD56 expression can define the cytotoxic effector subset among CD8 ϩ T cells (35) is also consistent with this notion, because most Ksp37-expressing T cells also expressed CD56 (data not shown). Moreover, the fact that Ksp37 is coexpressed with perforin strongly supports the above-described notion because perforin is a typical marker for cytotoxic lymphocytes (27,28,36). Coexpression of Ksp37 with perforin is also the case in ␥␦ T cells and even in CD4 ϩ T cells.…”

Section: Discussionsupporting

confidence: 59%

“…We further investigated Ksp37-expressing lymphocytes for expression levels of perforin, a pivotal molecule in granule-mediated cytotoxicity (27,28). In adult PBMCs, Ksp37 expression was associated with the expression of perforin in CD16 ϩ NK cells, CD8 ϩ T cells, ␥␦ T cells, and CD4 ϩ T cells, although expression levels of perforin in CD4 ϩ T cells were lower than those in the other three cell types (Fig.…”

Section: Figurementioning

confidence: 99%

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A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

Ogawa

Tanaka²,

Ishii³

et al. 2001

The Journal of Immunology

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Cytotoxic lymphocytes such as CTL and NK cells play principal roles in the host defense mechanisms. Monitoring these effector cells in vivo is helpful to understand the immune responses in disorders such as cancer and infectious diseases. In this study, we identified a novel secretory protein, killer-specific secretory protein of 37 kDa (Ksp37), as a Th1-specific protein by a subtractive cloning method between human Th1 and Th2 cells. In peripheral blood leukocytes, Ksp37 expression was limited to Th1-type CD4+ T cells, effector CD8+ T cells, γδ T cells, and CD16+ NK cells. Most of these Ksp37-expressing cells coexpressed perforin, indicating that Ksp37 is selectively and commonly expressed in the lymphocytes that have cytotoxic potential. Ksp37 was released at constant rate from both unstimulated and stimulated PBMCs in vitro and also detected in normal human sera. In healthy individuals, serum Ksp37 levels were significantly higher in children (mean ± SD; 984 ± 365 ng/ml for age 0–9) than in adults (441 ± 135 ng/ml for age 20–99), consistent with reported differences in the absolute counts of blood T and NK cells between children and adults. In patients with infectious mononucleosis, transient elevation of serum Ksp37 levels was observed during the early acute phase of primary EBV infection. These results suggest that Ksp37 may be involved in an essential process of cytotoxic lymphocyte-mediated immunity and that Ksp37 may also have clinical value as a new type of serum indicator for monitoring cytotoxic lymphocytes in vivo.

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Section: Discussionsupporting

confidence: 59%

Section: Figurementioning

confidence: 99%

A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

Ogawa

Tanaka²,

Ishii³

et al. 2001

The Journal of Immunology

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“…Once it is anchored, perforin begins the polymerization in the presence of Ca 2+ to form cylindrical pores with an internal diameter of 5 to 20 nm (63,65,66). The perforin pores can serve as passive conductos of granzymes and granulysin through the target cell membrane and could also allow an ionic exchange, which causes an osmotic unbalance and in consequence, the cell death ( Figure 2A) (65). However, in spite of this being the most accepted hypothesis, there is little experimental evidence to support it.…”

Section: Volume 6 Number 1 February 2009mentioning

confidence: 99%

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

et al. 2009

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One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8 + T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis. Cellular & Molecular Immunology. 2009;6(1):15-25.

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“…Memory and effector CD8 + T cells play an important role in viral eradication through their ability to produce various factors involved in suppression of viral replication [1][2][3][4] as well as in cytolysis of virus-infected cells [5,6]. Effector cytotoxic CD8 + T cells have the ability to kill target cells through perforin and Fas ligands.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic classification of human CD8⁺ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

et al. 2004

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Phenotypic classification of human CD8 + T cells using three cell surface markers, CD27, CD28 and CD45RA, was recently suggested to be useful for identification of naive, memory and effector CD8 + T cells. However, it still remains unclear whether such classification precisely reflects functional classification of CD8 + T cells. To clarify this, we characterized each CD27CD28CD45RA subset of total and human cytomegalovirus (HCMV)-specific CD8 + T cells by analyzing the expression of perforin and two chemokine receptors, CCR5 and CCR7, as well as their function. An inverse correlation between perforin and CD27 expression was found in all four CD28CD45RA subsets. Therefore, to achieve a phenotypic classification of CD8 + T cells that more precisely reflects their function, the CD27 + subset was divided into CD27 low and CD27 high subsets based on the expression level of CD27. Functional and flow cytometric analyses of CD27CD28CD45RA subsets showed that this phenotypic classification reflects functional classification of CD8 + T cells. HCMV-specific CD8 + T cells from healthy HCMV-seropositive individuals were predominantly found in effector and memory/effector subsets, indicating that HCMV-specific effector CD8 + T cells are actively induced by HCMV replication in healthy HCMV carriers. Phenotypic analyses of CD8 + T cells using this classification will enable the characterization of antigen-specific CD8 + T cells.

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Perforin: structure and function

Cited by 321 publications

References 80 publications

A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

Phenotypic classification of human CD8⁺ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

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Perforin: structure and function

Cited by 321 publications

References 80 publications

A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

A Novel Serum Protein That Is Selectively Produced by Cytotoxic Lymphocytes

Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

Phenotypic classification of human CD8+ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function

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Resources

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Phenotypic classification of human CD8⁺ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function