CD95-ligand (Fas-L)-expressing epidermal lymphocytes

Panfilis, G. De; Marcelli, Marco; Pasolini, G.; Torresani, Claudio

doi:10.1046/j.1365-2133.2000.03854.x

Cited by 6 publications

(5 citation statements)

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“…It is well established that the skin is commonly subjected to a variety of antigenic stimulations, and the immune system of the skin is able to respond to such stimuli by cutaneous immune responses, mainly sustained by activated specific T lymphocytes (32–34). On the other hand, as discussed above, although T cell proliferation and release of cytokines is critical for the cutaneous response to specific antigens, the expanded population of activated T cells must be decreased, to prevent accumulation of excessive numbers of harmful cytokine‐releasing lymphocytes, and one important homeostatic regulatory mechanism for peripheral activated T cells involves Fas‐/Fas‐L‐mediated AICD (26).…”

Section: Inflammatory Skin Diseases Can Be Associated With Activated mentioning

confidence: 99%

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

Panfilis¹

2002

Experimental Dermatology

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'Activation-induced cell death': a special program able to preserve the homeostasis of the skin?De Panfilis G. 'Activation-induced cell death': a special program able to Abstract: The 'activation-induced cell death' (AICD) is a molecular system leading to death of antigen-activated T lymphocytes, in order to avoid accumulation of harmful cytokine-releasing cells. This article reviews both the molecular mechanisms working in AICD and the role played by such mechanisms in preventing a number of skin diseases. Specifically, because AICD removes activated and autoreactive T cells through a CD95-/CD95-L-mediated suicide, skin diseases were scrutinized in which such valuable machinery could be lacking. Indeed, at least some inflammatory skin diseases, including psoriasis and atopic dermatitis, can be sustained by an increased survival of activated T lymphocytes associated with deficient CD95-/CD95-L-mediated AICD of such strong pro-inflammatory cells. In addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen planus and other lichenoid tissue reactions, can be related to autoreactive T lymphocytes which could be unable to AICD is likely to represent a fundamental program to preserve the homeostasis of the skin. Therapeutic approaches able to restore the AICD machinery promise to successfully treat such relevant skin diseases. Giuseppe De Panfilis Accepted for publication 18 June 2001 IntroductionEvidence is accumulating that cell death by apoptosis plays an important role in cutaneous biology and disease (reviewed in 1-5). Nevertheless, although in the past few years a large body of studies concerning the death receptors and molecular mechanisms involved in apoptosis have been carried out, our understanding of how these molecules act remains largely limited and is therefore difficult to translate the knowledge gained from these studies into clinical settings, including skin homeostasis and disease (1).However, at least one special apoptotic machine can be assessed, in our opinion, as playing a pivotal role to preserve the homeostasis of the skin, namely, the program termed 'activation-induced 1 cell death' (AICD). AICD, in fact, is an important mechanism for the regulation and limitation of cellular immune responses, in that antigen-reactivated T cells die, to prevent accumulation of excessive numbers of harmful cytokine-releasing T lymphocytes (reviewed in 6). The skin is indeed continuously challenged by a variety of antigenic stimuli, and a program should exist to prevent the perpetuous accumulation in the skin of expanded populations of antigen-reactive, activated T cells. Otherwise, activated/autoreactive T cells which are not removed after specific activation can persist within the skin, and may sustain inflammatory/autoreactive conditions. The aim of this review, therefore, was to explore the possible role played by AICD in preserving the homeostasis of the skin. If this was the case, in fact, molecular mechanisms work- De Panfilising in AICD should be defective in inflammatory/ autoreacti...

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Section: Inflammatory Skin Diseases Can Be Associated With Activated mentioning

confidence: 99%

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

Panfilis¹

2002

Experimental Dermatology

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“…The two controls for the mAb were positive, as occasional peripheral blood T lymphocytes were labelled (as detailed elsewhere), 24 and a proportion of epidermal lymphocytes were stained, as already reported. 25…”

Section: Controls For the Primary Antibody Are Positivementioning

confidence: 99%

Keratinocytes constitutively express the CD95 ligand molecule on the plasma membrane: an in situ immunoelectron microscopy study on ultracryosections of normal human skin

Panfilis¹,

Semenza

Llombart‐Bosch³

et al. 2002

Br J Dermatol

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Although scanty, the constitutive Fas-L expressed on the surface of KC can bind Fas expressed by possible occasional inflammatory cells entering the epidermis, and kill them, so preventing inflammation. Fas-L-expressing KC could moreover induce apoptosis of epidermal cells bearing viral or neoplastic antigens. Thus, the expression of Fas-L by KC may contribute to the preservation of epidermal homeostasis in vivo.

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“…On the other hand, both controls for the G247‐4 mAb gave positive results. In fact, both a proportion of epidermal lymphocytes (42) and occasional peripheral blood T lymphocytes (10) were demonstrated to be CD95‐L‐positive using such a mAb.…”

Section: Resultsmentioning

confidence: 99%

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

Panfilis

Venturini

Llombart‐Bosch³

et al. 2003

Experimental Dermatology

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Although dendritic cells (DC) are well known for their immunogenic capacities, they may even induce peripheral T-cell tolerance, and such a tolerogenic potential can be exerted in mouse through the expression on the DC plasma membrane of the CD95-ligand (CD95-L) molecule, which is able to trigger apoptosis of CD95-expressing antigen-specific T cells. We therefore asked whether epidermal DC, namely Langerhans' cells (LC), either resting (i.e. within the epidermis, 'in situ') or activated (i.e. suspended from the epidermis) or both, could express the CD95-L molecule on the plasma membrane. For such a purpose, two colloidal gold-immunoelectron microscopy (IEM) double-step procedures were carried out: an 'in situ' method, able to investigate resting LC, was performed on ultrathin frozen sections obtained by ultracryomicrotomy (UCMT) of normal skin biopsies; a pre-embedding (P-E) method, able to investigate suspended LC, was performed on epidermal cells (EC) suspended from normal skin specimens. In UCMT/IEM sections, resting LC showed gold particles within the cytoplasm but very rarely within organelles and never along the plasma membrane: resting LC are therefore capable of synthesizing CD95-L but not of expressing it in a functional location, thus autoreactive phenomena against CD95-expressing EC being avoided in normal epidermis. On the other hand, in P-E/IEM preparations, suspended LC showed several gold particles along the plasma membrane: activated LC are therefore capable of expressing CD95-L in a functional location, thus bearing the potential to exert tolerogenic capabilities against CD95-expressing T cells, e.g. to prevent inflammatory/autoimmune cutaneous disorders and/or favor the resolution thereof.

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CD95-ligand (Fas-L)-expressing epidermal lymphocytes

Cited by 6 publications

References 10 publications

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

Keratinocytes constitutively express the CD95 ligand molecule on the plasma membrane: an in situ immunoelectron microscopy study on ultracryosections of normal human skin

The tolerogenic molecule CD95‐L is expressed on the plasma membrane of human activated, but not resting, Langerhans' cells.

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