Expression of Bcl-XL Restores Cell Survival, but Not Proliferation and Effector Differentiation, in Cd28-Deficient T Lymphocytes

Dahl, Astrid M.; Klein, Christoph; Andres, Pietro G.; London, Cheryl A.; Lodge, Michael P.; Mulligan, Richard C.; Abbas, Abul K.

doi:10.1084/jem.191.12.2031

Cited by 53 publications

(50 citation statements)

References 23 publications

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“…Okkenhaug et al recently reported that distinct sequences in the intracellular portion of CD28 are responsible for the proliferative and for the anti-apoptotic functions of CD28-mediated costimulation [29]. Similarly, Dahl et al reported that constitutive expression of the anti-apoptotic molecule Bcl-x L was not able to compensate for the lack of costimulation [30], again suggesting that the proliferative and anti-apoptotic effects of CD28 are mediated independently.…”

Section: Discussionmentioning

confidence: 95%

The effects of B7‐dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration

et al. 2003

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We used 5-(and 6-) carboxyfluorescein diacetate succinimidyl ester -labeled TCRtransgenic CD4 + T cells to investigate the contribution of B7 costimulation to T cell activation and clonal expansion. B7 costimulation was blocked with the fusion protein cytotoxic T lymphocyte-associated antigen-4 (CTLA4)-Ig, which prevents the interaction of B7 with its receptor CD28 on T cells. CTLA4-Ig had different effects depending on the density of antigen (Ag)/MHC ligands available by T cells. In the presence of CTLA4-Ig, tenfold higher concentrations of Ag were required for T cells to undergo cell division in vitro. At high Ag concentrations, T cell division occurred at comparable rates whether in the presence or absence of CTLA4-Ig; however, T cell survival and clonal expansion were strongly inhibited. Addition of IL-2 restored T cell survival but not responsiveness to low doses of Ag. In vivo, B7 costimulation was similarly required for the survival of Ag-specific T cells but not for cell division in response to high amounts of Ag. Thus, B7 costimulation regulates CD4 + T cell responses by promoting cell division in the presence of limiting amounts of Ag, and by protecting T cells from the onset of apoptosis.

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Section: Discussionmentioning

confidence: 95%

The effects of B7‐dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration

et al. 2003

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“…CD28:B7 signaling is the best characterized and an important costimulatory pathway for naive T cell activation, including cytokine production, clonal expansion, and prevention of anergy and T cell survival (34,35). However, blocking CD28:B7 pathway wasn't effective in inducing tolerance to murine skin and islet transplantation (36,37).…”

Section: For a Review)mentioning

confidence: 99%

Activation of Adenosine 2A Receptors Attenuates Allograft Rejection and Alloantigen Recognition

Sevigny¹,

Li²,

Awad³

et al. 2007

The Journal of Immunology

129

101

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The current studies investigated the in vitro and in vivo effect of adenosine 2A receptor (A2AR) agonists to attenuate allogenic immune activation. We performed MLRs with spleen T lymphocytes and APCs isolated from wild-type and A2AR knockout mice of both C57BL/6 and BALB/c background strains. Two-way MLR-stimulated T cell proliferation was reduced by ATL313, a selective A2AR agonist in a dose-responsive manner (∼70%; 10 nM), an effect reversed by the A2AR antagonist ZM241385 (100 nM). By one-way MLRs, we observed that ATL313’s inhibitory effect was due to effects on both T cells and APCs. ATL313 suppressed the activation markers CD25 and CD40L and the release of inflammatory cytokines IFN-γ, RANTES, IL-12P70, and IL-2. ATL313 also increased negative costimulatory molecules programmed death-1 and CTLA-4 expressed on T cells. In lymphocytes activated with anti-CD3e mAb, ATL313 inhibited the phosphorylation of Zap70, an effect that was reversed by the protein kinase A inhibitor H-89. In skin transplants, allograft survival was enhanced with ATL313, an effect blocked by ZM241385. These results indicate that A2AR agonists attenuate allogenic recognition by action on both T lymphocytes and APCs in vitro and delayed acute rejection in vivo. We conclude that A2AR agonists may represent a new class of compounds for induction therapy in organ transplantation.

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“…In a double-blind, placebocontrolled, cross-over study [54] tremor was improved by theophylline (dose: 150 mg/day) in 80 % of patients (compared with 60 % of the propranolol-treated arm). One placebocontrolled small study has shown an effect of gabapentin (1800 mg and 3600 mg) [55], while another failed [56], and 1 small crossover study with propranolol has shown similar improvement for both drugs [57].…”

Section: Possibly Efficacious Drugsmentioning

confidence: 99%

The Treatment of Tremor

Schneider

Deuschl

2014

Neurotherapeutics

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Tremor is a hyperkinetic movement disorder characterized by rhythmic oscillations of one or more body parts. It can be disabling and may impair quality of life. Various etiological subtypes of tremor are recognized, with essential tremor (ET) and Parkinsonian tremor being the most common. Here we review the current literature on tremor treatment regarding ET and head and voice tremor, as well as dystonic tremor, orthostatic tremor, tremor due to multiple sclerosis (MS) or lesions in the brainstem or thalamus, neuropathic tremor, and functional (psychogenic) tremor, and summarize main findings. Most studies are available for ET and only few studies specifically focused on other tremor forms. Controlled trials outside ET are rare and hence most of the recommendations are based on a low level of evidence. For ET, propranolol and primidone are considered drugs of first choice with a mean effect size of approximately 50 % tremor reduction. The efficacy of topiramate is also supported by a large double-blind placebocontrolled trial, while other drugs have less supporting evidence. With a mean effect size of about 90 % deep brain stimulation in the nucleus ventralis intermedius or the subthalamic nucleus may be the most potent treatment; however, there are no controlled trials and it is reserved for severely affected patients. Dystonic limb tremor may respond to anticholinergics. Botulinum toxin improves head and voice tremor. Gabapentin and clonazepam are often recommended for orthostatic tremor. MS tremor responds only poorly to drug treatment. For patients with severe MS tremor, thalamic deep brain stimulation has been recommended. Patients with functional tremor may benefit from antidepressants and are best be treated in a multidisciplinary setting. Several tremor syndromes can already be treated with success. But new drugs specifically designed for tremor treatment are needed. ET is most likely covering different entities and their delineation may also improve treatment. Modern study designs and long-term studies are needed.

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Expression of Bcl-XL Restores Cell Survival, but Not Proliferation and Effector Differentiation, in Cd28-Deficient T Lymphocytes

Cited by 53 publications

References 23 publications

The effects of B7‐dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration

The effects of B7‐dependent costimulation on T cell division and survival in vivo and in vitro are dependent on antigen concentration

Activation of Adenosine 2A Receptors Attenuates Allograft Rejection and Alloantigen Recognition

The Treatment of Tremor

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