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Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Morita A, Werfel T, Stege H, Ahrens C, Karmann K, Grewe M, Grether-Beck S, Ruzicka T, Kapp A, Klotz LO, Sies H, Krutmann J - J. Exp. Med. (1997)

Bottom Line: In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin.In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation.These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.

ABSTRACT
Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.

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Semiquantitative assessment of apoptotic (○) and CD4+ (□)  cells in lesional skin of five patients with atopic dermatitis before, during  and after UVA phototherapy. Each time point was taken from each patient and the standard deviation for all time points was <15%.
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Figure 2: Semiquantitative assessment of apoptotic (○) and CD4+ (□) cells in lesional skin of five patients with atopic dermatitis before, during and after UVA phototherapy. Each time point was taken from each patient and the standard deviation for all time points was <15%.

Mentions: In all patients, UVA phototherapy led to a significant improvement of skin symptoms, as assessed by a clinical scoring system (total score before UVA phototherapy: 65.4 ± 6.2; total score after UVA phototherapy: 18.2 ± 3.4; P <0.001) (10). Skin specimens were analyzed for apoptotic cells using the TdT-mediated dUTP labeling (TUNEL) assay, followed by a anti-CD4 staining to detect T helper cells. Before therapy, numerous CD4+ cells were present intradermally in eczematous skin (3) (Fig. 1 A). This cell population did not contain a significant number of apoptotic cells, and this was in sharp contrast to specimens obtained from the same skin areas after UVA radiation therapy had been started. Already after the 1st UVA radiation exposure, CD4+, apoptotic cells were detected (Fig. 1 B). During subsequent UVA treatments, the number of double positive cells was further increased, whereas the total number of CD4+ cells decreased (Fig. 1, C and D and Fig. 2). After 10 exposures, the total number of intradermally located, CD4+ T cells had been significantly diminished, and most of the remaining cells showed signs of apoptosis (Fig. 2). No apoptotic cells were detected in the epidermal compartment (data not shown).


Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Morita A, Werfel T, Stege H, Ahrens C, Karmann K, Grewe M, Grether-Beck S, Ruzicka T, Kapp A, Klotz LO, Sies H, Krutmann J - J. Exp. Med. (1997)

Semiquantitative assessment of apoptotic (○) and CD4+ (□)  cells in lesional skin of five patients with atopic dermatitis before, during  and after UVA phototherapy. Each time point was taken from each patient and the standard deviation for all time points was <15%.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199141&req=5

Figure 2: Semiquantitative assessment of apoptotic (○) and CD4+ (□) cells in lesional skin of five patients with atopic dermatitis before, during and after UVA phototherapy. Each time point was taken from each patient and the standard deviation for all time points was <15%.
Mentions: In all patients, UVA phototherapy led to a significant improvement of skin symptoms, as assessed by a clinical scoring system (total score before UVA phototherapy: 65.4 ± 6.2; total score after UVA phototherapy: 18.2 ± 3.4; P <0.001) (10). Skin specimens were analyzed for apoptotic cells using the TdT-mediated dUTP labeling (TUNEL) assay, followed by a anti-CD4 staining to detect T helper cells. Before therapy, numerous CD4+ cells were present intradermally in eczematous skin (3) (Fig. 1 A). This cell population did not contain a significant number of apoptotic cells, and this was in sharp contrast to specimens obtained from the same skin areas after UVA radiation therapy had been started. Already after the 1st UVA radiation exposure, CD4+, apoptotic cells were detected (Fig. 1 B). During subsequent UVA treatments, the number of double positive cells was further increased, whereas the total number of CD4+ cells decreased (Fig. 1, C and D and Fig. 2). After 10 exposures, the total number of intradermally located, CD4+ T cells had been significantly diminished, and most of the remaining cells showed signs of apoptosis (Fig. 2). No apoptotic cells were detected in the epidermal compartment (data not shown).

Bottom Line: In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin.In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation.These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.

ABSTRACT
Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.

Show MeSH
Related in: MedlinePlus