Differential Susceptibility to HIV-GP120–Sensitized Apoptosis in CD4+ T-Cell Clones With Different T-Helper Phenotypes: Role of CD95/CD95L Interactions

Accornero, Paola; Radrizzani, Marina; Delia, Domenico; Gerosa, Franca; Kurrle, R.; Colombo, Mario P.

doi:10.1182/blood.v89.2.558

Cited by 47 publications

(43 citation statements)

References 59 publications

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“…Lesional skin of atopic dermatitis (AD) patients harbors activated T cells, and the relevant role subserved in the pathophysiology of the acute phases of AD by activated Th2 lymphocytes (52–54) may be due to lacking AICD of such cells (Table 3). In fact, Th2 clones were AICD resistant, because they failed to express high enough levels of Fas‐L molecules on the cell surface (55), and this was in agreement with previous reports (56,57). Similarly, very few T lymphocytes were apoptotic within mucosal biopsy specimens of patients with asthma (58).…”

Section: Inflammatory Skin Diseases Can Be Associated With Activated supporting

confidence: 91%

‘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 supporting

confidence: 91%

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

Panfilis¹

2002

Experimental Dermatology

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“…The effect of IL-16 on the inhibition of AICD may reflect a major difference in the outcome of signals transduced following CD4 ligation with different ligands. Cross-linking CD4 molecules with gp120 in the presence of anti-T cell receptor stimulation has been reported to increase AICD through a mechanism involving CD95/CD95 ligand interaction [32]. Similar results have also been obtained when anti-CD4 antibodies were used as the ligand [30,33].…”

Section: Discussionsupporting

confidence: 58%

Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD)

Idziorek

Khalife

Billaut-Mulot

et al. 1998

Clinical and Experimental Immunology

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The chemoattractant cytokine IL- 16 has been reported to suppress lymphocyte activation and to inhibit HIV-1 replication in acutely infected T cells. We have cloned and expressed human IL-16 in Escherichia coli and investigated whether the recombinant protein could regulate the level of lymphocyte apoptosis from HIV-1-infected subjects. After purification and refolding, only 2-10% of the recombinant cytokine was present in a biologically active homotetrameric form. This could explain the need for high concentrations of the bacterially derived IL- 16 to induce significant inhibition of HIV-1 replication. Addition of IL-16 to unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-1-infected subjects did not modify the observed level of spontaneous lymphocyte apoptosis. In contrast, IL-16 added to PBMC cultures stimulated with anti-CD3, anti-CD95 or dexamethasone reduced significantly the percentage of lymphocytes undergoing AICD. This effect was found to correlate with the ability of the cytokine to decrease CD95 expression on activated CD4+ T cells. Comparative studies on PBMC from healthy individuals indicated that the regulation of apoptosis levels by IL-16 is a complex phenomenon and could depend on the nature of the activator used and/or the immune status of lymphocytes tested. The outcome of CD4 cross-linking on T cells by various ligands is discussed in the context of the observed beneficial activities of IL- 16 and its potential role in the treatment of HIV disease.

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“…It has been shown by others that a Th2 phenotype would protect the cell from undergoing apoptosis [31][32][33][34][35][36][37][38][39][40][41][42][43]. We have shown in the present study that normal T cells in the presence of jacalin plus CD28 costimulation exhibit STAT-6 phosphorylation, as well as expression of Bcl-2 and Bcl-xL.…”

Section: Introductionsupporting

confidence: 66%

“…Our studies also indicate that the activation of p38 MAPK may protect cells from apoptosis by inducing IL-4 production and up-regulation of antiapoptotic markers Bcl-2 and Bcl-xL, as assessed by inclusion of the p38 MAPK inhibitor in the culture. Previous studies also support that blocking the CD28-B7 interaction blocks the induction of IL-4 synthesis, indicating that CD28 costimulation is important in regulation of IL-4 synthesis [4,11,36,50]. TCR-independent generation of Th2 effectors might provide a mechanism to control Th1-dominated cellular inflammation [44].…”

Section: Discussionmentioning

confidence: 76%

“…As it has been shown by previous studies that a Th2 phenotype would protect cells from undergoing apoptosis [31][32][33][34][35][36][37][38][39][40][41][42][43]45], we analyzed the expression of Bcl-2 and Bcl-xL in this culture system. We have shown in the present study that normal T cells in the presence of jacalin plus CD28 costimulation exhibit STAT-6 phosphorylation ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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p38 MAPK plays a role in IL-4 synthesis in jacalin plus CD28-stimulated CD4+ T cells—II

Tamma

Chung

Patel

et al. 2006

Journal of Leukocyte Biology

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We have previously shown that jacalin, a CD4+ T cell lectin, induces phosphorylation of intracellular events, moderate levels of interleukin (IL)-2 secretion. We have also shown that in the presence of CD28 costimulation, jacalin induces IL-4 secretion. In the present study, we showed that stimulation of normal CD4+ T cells with jacalin plus CD28 cross-linking (CD28XL) resulted in phosphorylation of signal transducer and activator of transcription (STAT)-6 and expression of Bcl-2 and Bcl-xL, which were inhibited significantly when cells were cultured in the presence of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. We further generated jacalin-induced CD4+ T cell blasts, examined the effects of CD28XL, and observed enhanced up-regulation of p38 and activation of STAT-6, Bcl-2, and Bcl-xL. Engagement of CD28 alone induced a marked degree of phosphorylation of p38 MAPK and IL-4 secretion in memory T cells (jacalin blasts), whereas in naïve T cells, jacalin plus CD28XL was required to induce these molecules. Incubation of cells with p38 inhibitor prior to CD28XL resulted in down-modulation of all these molecules. Further treatment with IL-4 has not reversed this trend. Our studies imply that p38 MAPK may play an important role in induction of these molecules and a putative role in protecting cells from undergoing apoptosis.

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Differential Susceptibility to HIV-GP120–Sensitized Apoptosis in CD4+ T-Cell Clones With Different T-Helper Phenotypes: Role of CD95/CD95L Interactions

Cited by 47 publications

References 59 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?

Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD)

p38 MAPK plays a role in IL-4 synthesis in jacalin plus CD28-stimulated CD4+ T cells—II

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