References of "Moutschen, Michel"
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See detailSubgroup and resistance analyses of raltegravir for resistant HIV-1 infection.
Cooper, David A; Steigbigel, Roy T; Gatell, Jose M et al

in New England Journal of Medicine [=NEJM] (2008), 359(4), 355-65

BACKGROUND: We evaluated the efficacy of raltegravir and the development of viral resistance in two identical trials involving patients who were infected with human immunodeficiency virus type 1 (HIV-1 ... [more ▼]

BACKGROUND: We evaluated the efficacy of raltegravir and the development of viral resistance in two identical trials involving patients who were infected with human immunodeficiency virus type 1 (HIV-1) with triple-class drug resistance and in whom antiretroviral therapy had failed. METHODS: We conducted subgroup analyses of the data from week 48 in both studies according to baseline prognostic factors. Genotyping of the integrase gene was performed in raltegravir recipients who had virologic failure. RESULTS: Virologic responses to raltegravir were consistently superior to responses to placebo, regardless of the baseline values of HIV-1 RNA level; CD4 cell count; genotypic or phenotypic sensitivity score; use or nonuse of darunavir, enfuvirtide, or both in optimized background therapy; or demographic characteristics. Among patients in the two studies combined who were using both enfuvirtide and darunavir for the first time, HIV-1 RNA levels of less than 50 copies per milliliter were achieved in 89% of raltegravir recipients and 68% of placebo recipients. HIV-1 RNA levels of less than 50 copies per milliliter were achieved in 69% and 80% of the raltegravir recipients and in 47% and 57% of the placebo recipients using either darunavir or enfuvirtide for the first time, respectively. At 48 weeks, 105 of the 462 raltegravir recipients (23%) had virologic failure. Genotyping was performed in 94 raltegravir recipients with virologic failure. Integrase mutations known to be associated with phenotypic resistance to raltegravir arose during treatment in 64 patients (68%). Forty-eight of these 64 patients (75%) had two or more resistance-associated mutations. CONCLUSIONS: When combined with an optimized background regimen in both studies, a consistently favorable treatment effect of raltegravir over placebo was shown in clinically relevant subgroups of patients, including those with baseline characteristics that typically predict a poor response to antiretroviral therapy: a high HIV-1 RNA level, low CD4 cell count, and low genotypic or phenotypic sensitivity score. (ClinicalTrials.gov numbers, NCT00293267 and NCT00293254.) [less ▲]

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See detailDecline of antibiotic use in primary care.
Frippiat, Frédéric ULg; Chandrikakumari, Kavitha; Moutschen, Michel ULg

in Lancet Infectious Diseases (2008), 8(5), 272273

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See detailLesions cerebrales demyelinisantes decouvertes chez un patient immunocompetent VIH-1+.
Nkoghe, D.; Moutschen, Michel ULg; Demonty, Jean ULg

in Médecine et Maladies Infectieuses (2008), 38(9), 500-3

We report the case of a 32-year-old immunocompetent HIV patient, presenting with acute demyelinating leukoencephalopathy. The patient displayed clinical and radiological features similar to multiple ... [more ▼]

We report the case of a 32-year-old immunocompetent HIV patient, presenting with acute demyelinating leukoencephalopathy. The patient displayed clinical and radiological features similar to multiple sclerosis. Histology revealed inflammation with necrosis, demyelination and destruction of axons. Serum tests were negative for various infectious agents as well as specific cultures and PCR. Corticotherapy and many antibiotic treatments failed. Resorption of the lesions occurred after partial excision and highly-active antiretroviral therapy (HAART). No recurrence was noted. This demyelinating cerebral disease was considered as the primary manifestation of HIV infection. HIV implication in the genesis of the process and its perpetuating this condition was suspected, but the mechanism is unclear. Dysimmune consequences related to the early course of HIV infection could be prevented by antiretroviral treatment. This study was the first description of tritherapy effectiveness on HIV related multiple sclerosis (MS)-like illness. [less ▲]

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See detailRecombinant gp350 vaccine for infectious mononucleosis: A phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults
Sokal, E. M.; Hoppenbrouwers, K.; Vandermeulen, C. et al

in Journal of Infectious Diseases (2007), 196(12), 1749-1753

Background. To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of ... [more ▼]

Background. To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus. Methods. A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen. Results. The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0% -96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for > 18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine. Conclusion. These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis. [less ▲]

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See detailPatients infectes par le VIH. Et syndrome lipodystrophique
Uurlings, Françoise ULg; Moutschen, Michel ULg

in Revue Médicale de Liège (2007), 62(11), 669-74

Prolonged utilization of some antiretroviral drugs in patients infected by HIV can lead to the outbreak of a lipodystrophy syndrome. This syndrome is characterized by modification of fats corporal ... [more ▼]

Prolonged utilization of some antiretroviral drugs in patients infected by HIV can lead to the outbreak of a lipodystrophy syndrome. This syndrome is characterized by modification of fats corporal repartition, sometimes associated with metabolic disturbancies (dyslipemia and insulin resistance). Two antiretroviral classes are implicated in the pathophysiology of this syndrome, namely protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs). The PIs rather influence the differentiation of adipose tissue with its secretion. They are more often associated with visceral adiposity, insulin resistance and dyslipemia. The mitochondrial toxicity of the NRTIs is more frequently responsible for adipose tissue loss at the periphery. Other factors in relation to the patient influence the severity of this syndrome. Several therapeutic options are to be considered both when taking care of the patients suffering from this syndrome and when new patients are to be treated. [less ▲]

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See detailA Patient with Hiv Infection, Cough, Asthenia, and Fever
Mayasi, N.; Chandrikakumari, Kavitha; Mukeba, D. et al

in Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America (2007), 45(5), 662-3559-600

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See detailPhase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults
Moutschen, Michel ULg; Leonard, Philippe ULg; Sokal, E. M. et al

in Vaccine (2007), 25(24), 4697-4705

Two double-blind randomised controlled studies (phase I and I/II) were performed to assess for the first time the safety and immunogenicity of a recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine ... [more ▼]

Two double-blind randomised controlled studies (phase I and I/II) were performed to assess for the first time the safety and immunogenicity of a recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine in 148 healthy adult volunteers. All candidate vaccine formulations had a good safety profile and were well tolerated, with the incidence of solicited and unsolicited symptoms within a clinically acceptable range. One serious adverse event was reported in the phase I trial which was considered to be of suspected relationship to vaccination. The gp350 vaccine formulations were immunogenic and induced gp350-specific antibody responses (including neutralising antibodies). (c) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailHIV-1 protease inhibitors do not interfere with provirus transcription and host cell apoptosis induced by combined treatment TNF-alpha plus TSA
Vandergeeten, Claire ULg; Quivy, Vincent; Moutschen, Michel ULg et al

in Biochemical Pharmacology (2007), 73(11), 1738-1748

HIV-1 latency represents a major hurdle to the complete eradication of the virus from patients under highly active anti-retroviral therapy (HAART) regimens. One solution to this problem would be to ... [more ▼]

HIV-1 latency represents a major hurdle to the complete eradication of the virus from patients under highly active anti-retroviral therapy (HAART) regimens. One solution to this problem would be to eliminate the latently infected cellular reservoirs by forcing gene expression in presence of HAART to prevent spreading of the infection by the newly synthesized viruses. Many studies have reported that a combination of a histone deacetylase inhibitor (HDACi) (i.e. TSA, NaBut, Valproic acid,...) with a pro-inflammatory cytokine (i.e. TNF alpha, IL-1,...) reactivates in a synergistic manner HIV-1 transcription in latently infected cells. The aim of the present study was to determine whether HIV-1 protease inhibitors (PIs) used in HAART (such as Saquinavir, Indinavir, Nelfinavir, Lopinavir, Ritonavir and Amprenavir) could interfere with the potential purge of the cellular reservoirs induced by a combined treatment involving TSA and TNF alpha. We showed, in two HIV-1 latently infected cell lines (ACH-2 and U1) that all PIs efficiently inhibited release of mature viral particles but did neither affect cell apoptosis nor NF-kappa B induction and HIV-1 transcription activation following combined treatment with TNF alpha + TSA. This study is encouraging in the fight against HIV-1 and shows that PIs should be compatible with an inductive adjuvent therapy for latent reservoir reduction/elimination in association with efficient HAART regimens. (c) 2007 Elsevier Inc. All rights reserved. [less ▲]

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See detailAvancees therapeutiques en pathologie infectieuse au cours de la derniere decennie
GIOT, Jean-Baptiste ULg; Mukeba Tshialala, D.; Mayasi Ngongo, N. et al

in Revue Médicale de Liège (2007), 62(5-6, May-Jun), 377-83

This review focuses on new antibiotics, particularly for gram-positive infections, new antiretroviral drugs, new treatment of fungal infections and indications of miltefosine in the treatment of ... [more ▼]

This review focuses on new antibiotics, particularly for gram-positive infections, new antiretroviral drugs, new treatment of fungal infections and indications of miltefosine in the treatment of leishmaniasis. [less ▲]

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See detailDownregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts.
Zeddou, Mustapha ULg; Rahmouni, Souad ULg; Vandamme, Arnaud ULg et al

in Retrovirology (2007), 4

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small ... [more ▼]

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells. [less ▲]

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See detailEvaluation clinique de la fonction du thymus.
Castermans, Emilie ULg; Morrhaye, Gabriel ULg; Marchand, S. et al

in Revue Médicale de Liège (2007), 62(11), 675-8

The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific ... [more ▼]

The essential role of the thymus is to install an extremely diverse repertoire of T lymphocytes that are self-tolerant and competent against non-self, as well as to generate self-antigen specific regulatory T cells (Treg) able to inactivate in periphery self-reactive T cells having escaped the thymic censorship. Although indirect, techniques of medical imaging and phenotyping of peripheral T cells may help in the investigation of thymic function. Nowadays however, thymopoiesis is better evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for the variable parts of the T-cell receptor for antigen (TCR). The TREC methodology is very valuable in the circumstances not associated with intense proliferation or apoptosis of peripheral T lymphocytes. [less ▲]

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See detailEvaluation de la thymopoiese: applications cliniques.
Castermans, Emilie ULg; Morrhaye, Gabriel ULg; Marchand, S. et al

in Revue Médicale de Liège (2007), 62(12), 725-9

In the precedent article, we have described how T-cell generation in the thymus (thymopoiesis) may be currently evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated ... [more ▼]

In the precedent article, we have described how T-cell generation in the thymus (thymopoiesis) may be currently evaluated through quantification by PCR of T-cell receptor excision circles (TREC) generated by intrathymic random recombination of the gene segments coding for variable parts of T-cell receptor for antigen (TCR). In hematology, TREC methodology helps in a better understanding of immune reconstitution after graft of hematopoietic stem cells: first there is a proliferation of mature T cells present in the graft, then a differentiation of naive T cells. In geriatrics, the homeostasis of the peripheral T-cell repertoire is maintained through proliferation of peripheral memory T cells rather than through thymic generation of naive T cells. In addition, TREC quantification constitutes a novel major tool for deciphering the tight control of thymopoiesis by the neuroendocrine system. [less ▲]

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See detailNouvelles approches dans la prise en charge de l'infection a VIH.
Chandrika, K.; Dellot, Patricia ULg; Frippiat, Frédéric ULg et al

in Revue Médicale de Liège (2007), 62 Spec No

HIV infection remains a major problem of public health in Belgium as well as globally. The number of new diagnosies of HIV infection in Belgium remains between two and three daily. Given the dramatic ... [more ▼]

HIV infection remains a major problem of public health in Belgium as well as globally. The number of new diagnosies of HIV infection in Belgium remains between two and three daily. Given the dramatic effect of antiretroviral therapy on the mortality due to HIV infection, the number of patients is constantly increasing. The different problems related to HIV care are also changing. Aging of the patients and chronic exposure to antiretroviral medications have induced new complications. We will present in this brief article several new experimental and clinical approaches in which our centre has participated during the last two years. [less ▲]

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See detailLoss of the VHR dual-specific phosphatase causes cell-cycle arrest and senescence
Rahmouni, Souad ULg; Cerignoli, Fabio; Alonso, Andres et al

in Nature Cell Biology (2006), 8(5), 524-178

Protein tyrosine phosphatases regulate important processes in eukaryotic cells and have critical functions in many human diseases including diabetes to cancer(1-3). Here, we report that the human Vaccinia ... [more ▼]

Protein tyrosine phosphatases regulate important processes in eukaryotic cells and have critical functions in many human diseases including diabetes to cancer(1-3). Here, we report that the human Vaccinia H1-related (VHR) dual-specific protein tyrosine phosphatase regulates cell-cycle progression and is itself modulated during the cell cycle. Using RNA interference (RNAi), we demonstrate that cells lacking VHR arrest at the G1-S and G2-M transitions of the cell cycle and show the initial signs of senescence, such as flattening, spreading, appearance of autophagosomes, beta-galactosidase staining and decreased telomerase activity. In agreement with this notion, cells lacking VHR were found to upregulate p21(Cip-Waf1), whereas they downregulated the expression of genes for cell-cycle regulators, DNA replication, transcription and mRNA processing. Loss of VHR also caused a several-fold increase in serum-induced activation of its substrates, the mitogen-activated protein ( MAP) kinases Jnk and Erk. VHR-induced cell-cycle arrest was dependent on this hyperactivation of Jnk and Erk, and was reversed by Jnk and Erk inhibition or knock-down. We conclude that VHR is required for cell-cycle progression as it modulates MAP kinase activation in a cell-cycle phase-dependent manner. [less ▲]

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See detailL'Hantavirose fait encore parler d'elle
Bourhaba, Maryam ULg; GIOT, Jean-Baptiste ULg; Tshialala, D. M. et al

in Revue Médicale de Liège (2006), 61(5-6, May-Jun), 322-8

We propose a review of history, aetiology, physiopathology, clinical features, treatment and prevention of nephropathia epidemica (NE) which represents the only form of Hantavirus infection in Belgium.

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See detailDoit-on encore recommander le vaccin BCG?
Collette, Georges ULg; Bourhaba, Maryam ULg; Moutschen, Michel ULg

in Revue Médicale de Liège (2006), 61(5-6, May-Jun), 430-2

The BCG vaccine has demonstrated its efficacy to protect young children from severe extrapulmonary forms of tuberculosis. Nevertheless, the immunity induced by the vaccine disappears in adults and cannot ... [more ▼]

The BCG vaccine has demonstrated its efficacy to protect young children from severe extrapulmonary forms of tuberculosis. Nevertheless, the immunity induced by the vaccine disappears in adults and cannot be boosted by readministration of BCG. Adverse effects of BCG are rare, but potentially dangerous (i.e. disseminated vaccinal infections) and they justify the fact that BCG should not be administered anymore in Western European countries where the incidence of pediatric tuberculous meningitis is very low. The vaccine is still recommanded for children living in countries with high tuberculosis prevalence and for resident children leaving Belgium for these countries. [less ▲]

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See detailRemoval of C-terminal Src kinase from the immune synapse by a new binding protein
Rahmouni, Souad ULg; Vang, Torkel; Alonso, Andres et al

in Molecular and Cellular Biology (2005), 25(6), 2227-2241

The Csk tyrosine kinase negatively regulates the Src family kinases Lek and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated ... [more ▼]

The Csk tyrosine kinase negatively regulates the Src family kinases Lek and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an similar to72-kDa tyrosine-phosphorylated protein, which we identify here as G3BP, a phosphoprotein reported to bind the SH3 domain of Ras GTPase-activating protein. G3BP reduced the ability of Csk to phosphorylate Lek at Y505 by decreasing the amount of Csk in lipid rafts. As a consequence, G3BP augmented T-cell activation as measured by interleukin-2 gene activation. Conversely, elimination of endogenous G3BP by RNA interference increased Lek Y505 phosphorylation and reduced TCR signaling. In antigen-specific T cells, endogenous G3BP moved into a intracellular location adjacent to the immune synapse, but deeper inside the cell, upon antigen recognition. Csk colocalization with G3BP occurred in this "parasynaptic" location. We conclude that G3BP is a new player in T-cell-antigen receptor signaling and acts to reduce the amount of Csk in the immune synapse. [less ▲]

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See detailAnomalies des cellules de l'immunite naturelle et risque infectieux chez le patient diabetique
Moutschen, Michel ULg

in Revue Médicale de Liège (2005), 60(5-6, May-Jun), 541-4

This review addresses the recent litterature devoted to the risk of severe infections in patients with diabetes and to the potential influence of diabetes on the function of natural immunity. Although ... [more ▼]

This review addresses the recent litterature devoted to the risk of severe infections in patients with diabetes and to the potential influence of diabetes on the function of natural immunity. Although much controversy still exists regarding the incidence of infections in diabetic patients, several studies confirm that diabetes mellitus is associated with an increased severity and mortality in community acquired pneumonia. Furthermore, the risk of severe bacteremia (especially associated with Streptococcus pneumoniae) is higher in diabetic patients. Polynuclear neutrophils are clearly influenced by the diabetic state. On the one hand, their antimicrobial function is inhibited by hyperglycaemia, due to inhibition of G6PD or diversion of NADPH in the polyol pathway; on the other hand, the AGE/RAGE/NF-kappaB pathway involved in the pathogenesis of chronic complications of diabetes could also amplify inflammatory systemic manifestations associated with infections and play a role in the higher mortality rate observed in diabetic subjects with severe infections. These observations argue for the systematic vaccination of all diabetic patients against influenza and Streptococcus pneumoniae, for the reappraisal of diabetes as a significant pejorative risk factor in community acquired pneumonia and for intensive insulin therapy in all diabetic patients with severe infection. [less ▲]

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See detailProstaglandin E2 induces the expression of functional inhibitory CD94/NKG2A receptors in human CD8+ T lymphocytes by a cAMP-dependent protein kinase A type I pathway.
Zeddou, Mustapha ULg; Greimers, Roland ULg; de Valensart, Nicolas et al

in Biochemical Pharmacology (2005), 70(5), 714-24

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small ... [more ▼]

The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated T cells, predominantly of CD8+ phenotype. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In an attempt to identify the mechanisms leading to inhibitory NKR upregulation on T cells, we analyzed the expression of the CD94/NKG2A heterodimer on human CTLs activated with anti-CD3 mAb in the presence of PGE2 or with 8-CPT-cAMP, an analogue of cyclic AMP. As previously described, anti-CD3 mAb-mediated activation induced the expression of CD94/NKG2A on a small fraction of CD8+ T cells. Interestingly, when low concentrations of PGE2 or 8-CPT-cAMP were present during the culture, the proportion of CD8+ T cells expressing CD94/NKG2A was two- to five-fold higher. This upregulation was partially prevented by PKA inhibitors, such as KT5720 and Rp-8-Br-cAMP (type I selective). We also report that cAMP induces upregulation of NKG2A at the mRNA level. We further demonstrated that cross-linking of CD94 on CD8+ T cells expressing the CD94/NKG2A heterodimer inhibits their cytotoxic activity in a bispecific antibody redirected lysis assay. Our findings clearly demonstrate that the PGE2/cAMP/PKA type I axis is involved in the expression of CD94/NKG2A receptor on human CD8+ T lymphocytes. [less ▲]

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