Expression of Fas Antigen on Keratinocytes In Vivo and Induction of Apoptosis in Cultured Keratinocytes

Sayama, Koji; Yonehara, Shin; Watanabe, Yûko; Miki, Yoshiharu

doi:10.1111/1523-1747.ep12394858

Cited by 164 publications

(116 citation statements)

References 37 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…7, allogeneic keratinocyte-specific CD4 ϩ T lymphocytes generated from the patient with perforin deficiency showed a low level of cytotoxicity against IFN-␥-treated keratinocytes. It has been reported that IFN-␥ treatment makes keratinocytes more sensitive to Fas-mediated apoptosis (37). On the basis of this previous report we examined whether cytotoxicity of CD4 ϩ T lymphocytes against IFN-␥-treated keratinocytes is mediated by the Fas-dependent pathway.…”

Section: T Lymphocytesmentioning

confidence: 98%

“…We next attempted to examine the cytotoxic mechanisms of CD4 ϩ CTLs against IFN-␥-treated keratinocytes, because IFN-␥-treated keratinocytes are known to be sensitive to Fas-mediated cytotoxicity (37). Four CD4 ϩ T lymphocyte bulk lines, four CD4 ϩ T lymphocyte clones, and three CD8 ϩ T lymphocyte bulk lines, four CD4 ϩ T lymphocyte bulk lines, three CD4 ϩ T lymphocyte clones, and three CD8 ϩ T lymphocyte bulk lines were established from T lymphocytes of the perforin-positive father and the perforin-deficient patient, respectively.…”

Section: Ifn-␥ Production By Alloantigen-specific T Lymphocytes In Rementioning

confidence: 99%

See 1 more Smart Citation

Essential Roles of Perforin in Antigen-Specific Cytotoxicity Mediated by Human CD4+ T Lymphocytes: Analysis Using the Combination of Hereditary Perforin-Deficient Effector Cells and Fas-Deficient Target Cells

Yanai

Ishii

Kojima

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Although the cytotoxic mechanisms of murine CTLs have been investigated extensively using various mutant and knockout mice, those of human CTLs, especially CD4 ؉ CTLs, are still obscure. To clarify the roles of perforin in Ag-specific cytotoxicity mediated by human CD4 ؉ CTLs, alloantigen-specific and HSV-specific human CD4 ؉ T lymphocyte bulk lines and clones were established from a patient with hereditary perforin deficiency and her healthy father, and their cytotoxic activities were investigated. Alloantigen-specific CD4 ؉ T lymphocytes expressing perforin exerted cytotoxicity against Fas-negative as well as Fas-positive allogeneic B lymphoblastoid cell lines established from members of a family with hereditary Fas deficiency. Perforin-deficient, but not perforin-expressing, CD4؉ T lymphocytes failed to show strong cytotoxicity against HSV-infected autologous B lymphoblastoid cells. Perforin-deficient CD4؉ T lymphocytes could exert relatively low level cytotoxicity against allogeneic IFN-␥-treated keratinocytes. Although cytotoxicity mediated by perforin-expressing CD4 ؉ CTLs was almost completely inhibited by concanamycin A, a potent inhibitor of the perforin-mediated cytotoxic pathway, cytotoxicity against IFN-␥-treated keratinocytes mediated by perforin-deficient CD4 ؉ T lymphocytes was inhibited only partially by concanamycin A, but was inhibited significantly by antagonistic anti-Fas Ab and anti-Fas ligand Ab. The combination of perforin-deficient effector T lymphocytes and Fas-negative target cells used in the present study provides a novel experimental system for studying the detailed mechanisms of human CTL-mediated cytotoxicity. The present data demonstrate that perforin-negative CD4 ؉ CTLs can exert cytotoxicity against Fas-sensitive target cells; however, perforin plays essential roles in Ag-specific cytotoxicity mediated by human CD4؉ as well as CD8 ؉

show abstract

Section: T Lymphocytesmentioning

confidence: 98%

Section: Ifn-␥ Production By Alloantigen-specific T Lymphocytes In Rementioning

confidence: 99%

Essential Roles of Perforin in Antigen-Specific Cytotoxicity Mediated by Human CD4+ T Lymphocytes: Analysis Using the Combination of Hereditary Perforin-Deficient Effector Cells and Fas-Deficient Target Cells

Yanai

Ishii

Kojima

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The discussion about whether death receptors are involved in UV-induced apoptosis arose when it was recognized that keratinocytes express the CD95 receptor (38,39). Accordingly, UVC radiation was found to upregulate both CD95 and its natural ligand CD95L in primary keratinocytes (40).…”

Section: Death Receptors On the Cell Membrane Are Involved In Uv-indumentioning

confidence: 99%

Molecular mechanisms of UV‐induced apoptosis

Kulms

Schwarz

2000

Photoderm Photoimm Photomed

281

206

View full text Add to dashboard Cite

Sunburn cells, single standing cells with typical morphologic features occurring in UV-exposed skin, have been recognized as keratinocytes undergoing apoptosis following UV irradiation. Induction of apoptosis following UV exposure appears to be a protective mechanism, getting rid off severely damaged cells that bear the risk of malignant transformation. UV-mediated apoptosis is a highly complex process in which different molecular pathways are involved. These include DNA damage, activation of the tumor suppressor gene p53, triggering of cell death receptors

show abstract

“…Keratinocytes, under the influence of lymphocytederived cytokines such as IFN-␥ and IL-17, also express MHC class II and adhesion molecules (ICAM-1) crucial for T cell function and retention in the epidermis (17,26). Moreover, IFN-␥ upregulates Fas expression and renders keratinocytes sensitive to Fas-mediated lysis (27,28).…”

Section: A Llergic Contact Dermatitis (Acd)mentioning

confidence: 99%

Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes

Traidl

Sebastiani

Albanesi

et al. 2000

The Journal of Immunology

138

115

View full text Add to dashboard Cite

Allergic contact dermatitis (ACD) is the result of an exaggerated immune reaction to haptens mediated by skin-homing T cells, but the effector mechanisms responsible for the tissue damage are poorly understood. Here we studied the capacity of distinct subsets of hapten-specific T cells to induce apoptosis in autologous keratinocytes. Skin- and blood-derived nickel-specific CD8+ T cytotoxic 1 (Tc1) and Tc2 clones as well as CD4+ Th1 and Th2 expressed the cutaneous lymphocyte-associated Ag and exhibited strong MHC-restricted cytotoxicity against nickel-coupled B lymphoblasts, as detected by the [3H]TdR release assay. Both Tc1 and Tc2 clones, but not CD4+ T cells, displayed a significant cytotoxic activity against resting nickel-modified keratinocytes. Following IFN-γ treatment, keratinocytes expressed MHC class II and ICAM-1 and became susceptible to Th1-mediated, but not Th2-mediated, cytotoxicity. The molecules of the two major cytotoxic pathways, Fas ligand (FasL) and perforin, were expressed by Tc1, Tc2, and Th1 cells, whereas Th2 cells expressed only FasL. Experiments performed in the presence of specific inhibitors of the perforin (concanamycin A) and FasL (brefeldin A) pathway indicated that perforin-mediated killing dominated in Tc1 and Tc2, and FasL-mediated cytotoxicity prevailed in Th2 clones, with a more heterogeneous behavior in the case of Th1 cells. Finally, perforin mRNA was expressed in ACD lesional skin, as assessed by RT-PCR analysis. In aggregate, our results indicate that keratinocytes can be target of multiple hapten-specific CTL responses, that may have distinct roles in the epidermal injury during ACD.

show abstract

Expression of Fas Antigen on Keratinocytes In Vivo and Induction of Apoptosis in Cultured Keratinocytes

Cited by 164 publications

References 37 publications

Essential Roles of Perforin in Antigen-Specific Cytotoxicity Mediated by Human CD4+ T Lymphocytes: Analysis Using the Combination of Hereditary Perforin-Deficient Effector Cells and Fas-Deficient Target Cells

Essential Roles of Perforin in Antigen-Specific Cytotoxicity Mediated by Human CD4+ T Lymphocytes: Analysis Using the Combination of Hereditary Perforin-Deficient Effector Cells and Fas-Deficient Target Cells

Molecular mechanisms of UV‐induced apoptosis

Disparate Cytotoxic Activity of Nickel-Specific CD8+ and CD4+ T Cell Subsets Against Keratinocytes

Contact Info

Product

Resources

About