Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes

Kojima, Hiroko; Shinohara, Nobukata; Hanaoka, Satoko; Someya-Shirota, Yoshiko; Takagaki, Yohtaroh; Ohno, Hiroshi; Saito, Takashi; Katayama, Takashi; Yagita, Hideo; Okumura, Ko; Shinkai, Yoichi; Alt, Frederick W.; Matsubara, Akio; Yonehara, Shin; Takayama, Hajime

doi:10.1016/1074-7613(94)90066-3

Cited by 282 publications

(162 citation statements)

References 37 publications

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“…On the other hand, although CD8 ϩ CD45RA ϩ CD27 Ϫ T cells contain FasL mRNA (7) and express limited but discernible amounts of FasL intracellularly, we were unable, even in the presence of specific proteinase inhibitors, to reliably demonstrate FasL on the surface of effector cells. However, the contribution of FasL in the induction of apoptosis in a Fas-sensitive Burkitt lymphoma line demonstrates that, in accordance with previous findings in mice (38,39), in vivo matured human CTLs can make use of the FasL effector pathway…”

Section: Discussionsupporting

confidence: 90%

Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27− Human T Cells

Baars

Couto

Leusen

et al. 2000

The Journal of Immunology

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Circulating CD8+ T cells with a CD45RA+CD27− phenotype resemble cytolytic effector cells because they express various cytolytic mediators and are able to execute cytotoxicity without prior stimulation in vitro. We here demonstrate that CD8+CD45RA+CD27− T cells can use both granule exocytosis and Fas/Fas ligand pathways to induce apoptosis in target cells. The availability of these cytolytic mechanisms in circulating T cells suggests that the activity of these cells must be carefully controlled to prevent unwanted tissue damage. For this reason, we analyzed the expression of surface receptors that either enhance or inhibit T cell function. Compared with memory-type cells, effector cells were found to express normal levels of CD3ε and TCRζ and relatively high levels of CD8. CTLA-4 was absent from freshly isolated effector cells, whereas a limited number of unstimulated memory cells expressed this molecule. In line with recent findings on CD8+CD28− T cells, CD45RA+CD27− T cells were unique in the abundant expression of NK cell-inhibitory receptors, both of Ig superfamily and C-type lectin classes. Binding of NK cell-inhibitory receptors to classical and nonclassical MHC class I molecules may inhibit the activation of the cytolytic machinery induced by either Ag receptor-specific or nonspecific signals in CD8+CD45RA+CD27− T cells.

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Section: Discussionsupporting

confidence: 90%

Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27− Human T Cells

Baars

Couto

Leusen

et al. 2000

The Journal of Immunology

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“…CTL recognition of target cells through their T-cell receptors activates 2 distinct mechanisms of cell lysis. 31,32 The first is granule exocytosis mediated by the pore-forming perforin and granzyme A and B. The second involves interaction between the Fas ligand on effector cells and Fas molecules expressed on the target cells.…”

Section: Discussionmentioning

confidence: 99%

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Wen

Barlogie

2001

Blood

116

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“…In turn, these mediators can cause tissue destruction through the upregulation of matrix metalloproteinase (MMP) production by macrophages and other immune effectors (Grumelli et al 2004;Manneo 2007). CD8 + T-lymphocytes can also mediate cell-death directly through the secretion of cytotoxic mediators (eg, granzyme and perforins), as well as expression or secretion of Fas (Henkart 1994;Kojima et al 1994). While the function of CD8 + lymphocytes are often highlighted in COPD studies, the potential contributions of CD4 + T-cells in the disease process also appear to be substantial.…”

Section: Cd4/cd8 T-cell Subsets In Copdmentioning

confidence: 99%

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

Gadgil

Duncan

2008

COPD

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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the US and a major worldwide healthcare problem. The pathophysiologic mechanisms that drive development and progression of this disease are complex and only poorly understood. While tobacco smoking is the primary risk factor, other disease processes also appear to play a role. Components of the innate immune system (eg, macrophages and neutrophils) have long been believed to be important in the development of COPD. More recent evidence also suggests involvement of the adaptive immune system in pathogenesis of this disease. Here we will review the literature supporting the participation of T-cells in the development of COPD, and comment on the potential antigenic stimuli that may account for these responses. We will further explore the prospective contributions of T-cell derived mediators that could contribute to the infl ammation, alveolar wall destruction, and small airway fi brosis of advanced COPD. A better understanding of these complex immune processes will lead to new insights that could result in improved preventative and/or treatment strategies.

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Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes

Cited by 282 publications

References 37 publications

Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27− Human T Cells

Cytolytic Mechanisms and Expression of Activation-Regulating Receptors on Effector-Type CD8+CD45RA+CD27− Human T Cells

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Role of T-lymphocytes and pro-inflammatory mediators in the pathogenesis of chronic obstructive pulmonary disease

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