Summary Staphylococcus aureus is an important pathogen that continues to be a significant global ... more Summary Staphylococcus aureus is an important pathogen that continues to be a significant global health threat because of the prevalence of methicillin-resistant S. aureus strains (MRSA). The pathogenesis of this organism is partly attributed to the production of a large repertoire of cytotoxins that target and kill innate immune cells, which provide the first line of defence against S. aureus infection. Here we demonstrate that leukocidin A/B (LukAB) is required and sufficient for the ability of S.
Abstract CD4+CD25+Foxp3+ Regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have e... more Abstract CD4+CD25+Foxp3+ Regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M.
Abstract CC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels a... more Abstract CC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels are a critical determinant of HIV-1 infection. However, the molecular mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite binding to conserved DNA elements, we show that the transcription factors GATA binding protein 1 (GATA-1) and GATA-3 differentially suppress the expression of CCR5 in stem-cell–derived dendritic cells and primary human T-cell subsets.
ABSTRACT Human CD4+ T cells are major targets for human immunodeficiency virus (HIV) infection. R... more ABSTRACT Human CD4+ T cells are major targets for human immunodeficiency virus (HIV) infection. Resting T cells are resistant to HIV infection unless activated through the T-cell receptor (TCR) or by cytokine signals. How T-cell signaling promotes susceptibility of T cells to HIV infection remains poorly understood. Here we demonstrate that the VacA toxin produced by Helicobacter pylori can inhibit HIV infection of primary T cells, stimulated through the TCR or by cytokines alone.
Abstract Introduction: Mitochondrial function influences T cell dynamics and is affected by mitoc... more Abstract Introduction: Mitochondrial function influences T cell dynamics and is affected by mitochondrial DNA (mtDNA) variation. We previously reported an association between African mtDNA haplogroup L2 and less robust CD4 cell recovery on antiretroviral therapy (ART) in non-Hispanic black ACTG 384 subjects. We explored whether additional T cell parameters in this cohort differed by mtDNA haplogroup.
Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. How... more Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy.
APOBEC3G (hA3G) and APOBEC3F (hA3F) evolved to limit retro-transposition1-4 and the replication o... more APOBEC3G (hA3G) and APOBEC3F (hA3F) evolved to limit retro-transposition1-4 and the replication of mammalian retroviruses. They significantly diminish the infectivity of HIV-1 when packaged into budding virions in the producer cell5. HIV-1 Vif binds to hA3G/F and causes the proteosomal degradation of hA3G/F6, 7, thus leading to decreased virion packaging of the enzymes.
Regulatory T cells (Tregs) suppress immune activation and are critical in preventing autoimmune d... more Regulatory T cells (Tregs) suppress immune activation and are critical in preventing autoimmune diseases. While the ability of Tregs to inhibit proliferation of other T cells is well established, it is not yet clear whether Tregs also modulate inflammatory cytokines during an immune response. Here, we show that the expression of inflammatory cytokine receptors IL-1R1 and TNFR2 were higher on resting mature Tregs compared to naïve or memory T cells.
ABSTRACT Several members of the chemokine receptor family have recently been identified as corece... more ABSTRACT Several members of the chemokine receptor family have recently been identified as coreceptors, with CD4, for entry of human immunodeficiency virus type 1 (HIV-1) into target cells. In this report, we show that the envelope glycoproteins of several strains of HIV-2 and simian immunodeficiency virus (SIV) employ the same chemokine receptors for infection. Envelope glycoproteins from HIV-2 use CCR5 or CXCR4, while those from several strains of SIV use CCR5.
Recently, several groups reported that NKT cells that express CD4 and CCR5 are highly susceptible... more Recently, several groups reported that NKT cells that express CD4 and CCR5 are highly susceptible to HIV infection and are depleted in HIV-infected individuals.2-4 Given the important role of NKT cells in potentially linking innate to adaptive immune responses, their loss in HIV-infected subjects may have several pathologic consequences, including impaired responses to opportunistic infections and tumors.
Exogenous retroviruses are obligate cellular parasites that co-opt a number of host proteins and ... more Exogenous retroviruses are obligate cellular parasites that co-opt a number of host proteins and functions to enable their replication and spread. Several host factors that restrict HIV and other retroviral infections have also recently been described. Here we demonstrate that Mov10, a protein associated with P-bodies that has a putative RNA-helicase domain, when overexpressed in cells can inhibit the production of infectious retroviruses.
Background: According to the international consensus statement on antiphospholipid syndrome (APS)... more Background: According to the international consensus statement on antiphospholipid syndrome (APS), antiphospholipid antbodies (aPL) of the IgG or the IgM isotype have to be positive for the classification of APS. The IgA isotype (either anticardiolipin antibodies [aCL] or anti-β2-glycoprotein I antibodies [antiβ2GPI]) do not fulfil laboratory criteria for APS classification. However, they are discussed in the consensus paper.
HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the ret... more HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the retroviral preintegration complex (PIC), into the nucleus. Too large for passive diffusion through nuclear pore complexes (NPCs), PICs use cellular nuclear transport mechanisms and nucleoporins (NUPs), the NPC components that permit selective nuclear-cytoplasmic exchange, but the details remain unclear. Here we identify a fragment of the cleavage and polyadenylation factor 6, CPSF6, as a potent inhibitor of HIV-1 infection.
Abstract Chronic immune activation is a hallmark of HIV infection, yet the underlying triggers of... more Abstract Chronic immune activation is a hallmark of HIV infection, yet the underlying triggers of immune activation remain unclear. Persistent antigenic stimulation during HIV infection may also lead to immune exhaustion, a phenomenon in which effector T cells become dysfunctional and lose effector functions and proliferative capacity.
Abstract Surface levels of CCR5 on memory CD4+ T cells influence HIV-1/AIDS susceptibility. Alter... more Abstract Surface levels of CCR5 on memory CD4+ T cells influence HIV-1/AIDS susceptibility. Alternative promoter usage results in the generation of CCR5 mRNA isoforms that differ based on whether they contain or lack the untranslated exon 1. The impact of exon 1-containing transcripts on CCR5 surface expression is unknown. In this study, we show that the increased cell surface expression of CCR5 on primary T cells is associated with selective enrichment of exon 1-containing transcripts.
Abstract Background: A poor vitamin D status has been associated with a high disease activity of ... more Abstract Background: A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.
Abstract Human memory T cells (TM cells) that produce IL-17 or IL-22 are currently defined as Th1... more Abstract Human memory T cells (TM cells) that produce IL-17 or IL-22 are currently defined as Th17 or Th22 cells, respectively. These T cell lineages are almost exclusively CCR6+ and are important mediators of chronic inflammation and autoimmunity. However, little is known about the mechanisms controlling IL-17/IL-22 expression in memory Th17/Th22 subsets.
Abstract CD56, an adhesion molecule closely related to neual cell adhesion molecule, is an immuno... more Abstract CD56, an adhesion molecule closely related to neual cell adhesion molecule, is an immunophenotypic marker for several unique populations of PBLs. Although CD56+ cells derive from multiple lymphocyte lineages, they share a role in immunosurveillance and antitumor responses. We have studied the chemokine receptor expression patterns and functional migratory responses of three distinct CD56+ populations from human peripheral blood.
Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. O... more Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections.
Summary Staphylococcus aureus is an important pathogen that continues to be a significant global ... more Summary Staphylococcus aureus is an important pathogen that continues to be a significant global health threat because of the prevalence of methicillin-resistant S. aureus strains (MRSA). The pathogenesis of this organism is partly attributed to the production of a large repertoire of cytotoxins that target and kill innate immune cells, which provide the first line of defence against S. aureus infection. Here we demonstrate that leukocidin A/B (LukAB) is required and sufficient for the ability of S.
Abstract CD4+CD25+Foxp3+ Regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have e... more Abstract CD4+CD25+Foxp3+ Regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M.
Abstract CC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels a... more Abstract CC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels are a critical determinant of HIV-1 infection. However, the molecular mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite binding to conserved DNA elements, we show that the transcription factors GATA binding protein 1 (GATA-1) and GATA-3 differentially suppress the expression of CCR5 in stem-cell–derived dendritic cells and primary human T-cell subsets.
ABSTRACT Human CD4+ T cells are major targets for human immunodeficiency virus (HIV) infection. R... more ABSTRACT Human CD4+ T cells are major targets for human immunodeficiency virus (HIV) infection. Resting T cells are resistant to HIV infection unless activated through the T-cell receptor (TCR) or by cytokine signals. How T-cell signaling promotes susceptibility of T cells to HIV infection remains poorly understood. Here we demonstrate that the VacA toxin produced by Helicobacter pylori can inhibit HIV infection of primary T cells, stimulated through the TCR or by cytokines alone.
Abstract Introduction: Mitochondrial function influences T cell dynamics and is affected by mitoc... more Abstract Introduction: Mitochondrial function influences T cell dynamics and is affected by mitochondrial DNA (mtDNA) variation. We previously reported an association between African mtDNA haplogroup L2 and less robust CD4 cell recovery on antiretroviral therapy (ART) in non-Hispanic black ACTG 384 subjects. We explored whether additional T cell parameters in this cohort differed by mtDNA haplogroup.
Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. How... more Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy.
APOBEC3G (hA3G) and APOBEC3F (hA3F) evolved to limit retro-transposition1-4 and the replication o... more APOBEC3G (hA3G) and APOBEC3F (hA3F) evolved to limit retro-transposition1-4 and the replication of mammalian retroviruses. They significantly diminish the infectivity of HIV-1 when packaged into budding virions in the producer cell5. HIV-1 Vif binds to hA3G/F and causes the proteosomal degradation of hA3G/F6, 7, thus leading to decreased virion packaging of the enzymes.
Regulatory T cells (Tregs) suppress immune activation and are critical in preventing autoimmune d... more Regulatory T cells (Tregs) suppress immune activation and are critical in preventing autoimmune diseases. While the ability of Tregs to inhibit proliferation of other T cells is well established, it is not yet clear whether Tregs also modulate inflammatory cytokines during an immune response. Here, we show that the expression of inflammatory cytokine receptors IL-1R1 and TNFR2 were higher on resting mature Tregs compared to naïve or memory T cells.
ABSTRACT Several members of the chemokine receptor family have recently been identified as corece... more ABSTRACT Several members of the chemokine receptor family have recently been identified as coreceptors, with CD4, for entry of human immunodeficiency virus type 1 (HIV-1) into target cells. In this report, we show that the envelope glycoproteins of several strains of HIV-2 and simian immunodeficiency virus (SIV) employ the same chemokine receptors for infection. Envelope glycoproteins from HIV-2 use CCR5 or CXCR4, while those from several strains of SIV use CCR5.
Recently, several groups reported that NKT cells that express CD4 and CCR5 are highly susceptible... more Recently, several groups reported that NKT cells that express CD4 and CCR5 are highly susceptible to HIV infection and are depleted in HIV-infected individuals.2-4 Given the important role of NKT cells in potentially linking innate to adaptive immune responses, their loss in HIV-infected subjects may have several pathologic consequences, including impaired responses to opportunistic infections and tumors.
Exogenous retroviruses are obligate cellular parasites that co-opt a number of host proteins and ... more Exogenous retroviruses are obligate cellular parasites that co-opt a number of host proteins and functions to enable their replication and spread. Several host factors that restrict HIV and other retroviral infections have also recently been described. Here we demonstrate that Mov10, a protein associated with P-bodies that has a putative RNA-helicase domain, when overexpressed in cells can inhibit the production of infectious retroviruses.
Background: According to the international consensus statement on antiphospholipid syndrome (APS)... more Background: According to the international consensus statement on antiphospholipid syndrome (APS), antiphospholipid antbodies (aPL) of the IgG or the IgM isotype have to be positive for the classification of APS. The IgA isotype (either anticardiolipin antibodies [aCL] or anti-β2-glycoprotein I antibodies [antiβ2GPI]) do not fulfil laboratory criteria for APS classification. However, they are discussed in the consensus paper.
HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the ret... more HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the retroviral preintegration complex (PIC), into the nucleus. Too large for passive diffusion through nuclear pore complexes (NPCs), PICs use cellular nuclear transport mechanisms and nucleoporins (NUPs), the NPC components that permit selective nuclear-cytoplasmic exchange, but the details remain unclear. Here we identify a fragment of the cleavage and polyadenylation factor 6, CPSF6, as a potent inhibitor of HIV-1 infection.
Abstract Chronic immune activation is a hallmark of HIV infection, yet the underlying triggers of... more Abstract Chronic immune activation is a hallmark of HIV infection, yet the underlying triggers of immune activation remain unclear. Persistent antigenic stimulation during HIV infection may also lead to immune exhaustion, a phenomenon in which effector T cells become dysfunctional and lose effector functions and proliferative capacity.
Abstract Surface levels of CCR5 on memory CD4+ T cells influence HIV-1/AIDS susceptibility. Alter... more Abstract Surface levels of CCR5 on memory CD4+ T cells influence HIV-1/AIDS susceptibility. Alternative promoter usage results in the generation of CCR5 mRNA isoforms that differ based on whether they contain or lack the untranslated exon 1. The impact of exon 1-containing transcripts on CCR5 surface expression is unknown. In this study, we show that the increased cell surface expression of CCR5 on primary T cells is associated with selective enrichment of exon 1-containing transcripts.
Abstract Background: A poor vitamin D status has been associated with a high disease activity of ... more Abstract Background: A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.
Abstract Human memory T cells (TM cells) that produce IL-17 or IL-22 are currently defined as Th1... more Abstract Human memory T cells (TM cells) that produce IL-17 or IL-22 are currently defined as Th17 or Th22 cells, respectively. These T cell lineages are almost exclusively CCR6+ and are important mediators of chronic inflammation and autoimmunity. However, little is known about the mechanisms controlling IL-17/IL-22 expression in memory Th17/Th22 subsets.
Abstract CD56, an adhesion molecule closely related to neual cell adhesion molecule, is an immuno... more Abstract CD56, an adhesion molecule closely related to neual cell adhesion molecule, is an immunophenotypic marker for several unique populations of PBLs. Although CD56+ cells derive from multiple lymphocyte lineages, they share a role in immunosurveillance and antitumor responses. We have studied the chemokine receptor expression patterns and functional migratory responses of three distinct CD56+ populations from human peripheral blood.
Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. O... more Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections.
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Papers by Derya Unutmaz