Paul Klenerman

Large scale analysis of pediatric antiviral CD8+ T cell populations reveals sustained, functional and mature responses (2006)

Komatsu, Haruki, Inui, Ayano, Sogo, Tsuyoshi, Fujisawa, Tomoo, Nagasaka, Hironori, Nonoyama, Shigeaki, ...

Abstract Background Cellular immunity plays a crucial role in cytomegalovirus (CMV) infection and substantial populations of CMV-specific T cells accumulate throughout life. However, although CMV...

Prolonged Activation of Virus-Specific CD8+T Cells after Acute B19 Infection (2005)

Adiba Isa, Victoria Kasprowicz, Oscar Norbeck, Andrew Loughry, Katie Jeffery, Kristina Broliden, ...

Although parvovirus B19 apparently causes an acute viral infection, it appears to induce a persistent activated CD8 + T cell response.

Prolonged Activation of Virus-Specific CD8+T Cells after Acute B19 Infection (2005)

Adiba Isa, Victoria Kasprowicz, Oscar Norbeck, Andrew Loughry, Katie Jeffery, Kristina Broliden, ...

Background Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The...

Viral persistence in vivo through selection of neutralizing antibody-escape variants

Ciurea, Adrian, Klenerman, Paul, Hunziker, Lukas, Horvath, Edit, Senn, Beatrice M., Ochsenbein, Adrian F., ...

Despite initial virus control by CD8+ cytotoxic T lymphocytes (CTLs), noncytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HIV) are able to establish persistent infections....

A comparison of T cell memory against the same antigen induced by virus versus intracellular bacteria

Ochsenbein, Adrian F., Karrer, Urs, Klenerman, Paul, Althage, Alana, Ciurea, Adrian, Shen, Hao, ...

Cytotoxic T cell (CTL) memory was analyzed after infection with lymphocytic choriomeningitis virus (LCMV) and recombinant Listeria monocytogenes (rLM) expressing the complete nucleoprotein of LCMV...

Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice

Ciurea, Adrian, Klenerman, Paul, Hunziker, Lukas, Horvath, Edit, Odermatt, Bernhard, Ochsenbein, Adrian F., ...

Lymphocytic choriomeningitis virus (LCMV), strain WE, is a non-cytopathic RNA virus that is highly adapted to its natural host, the mouse. Acute infection of adult mice leads to generalized virus...

Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection

Price, David A., Goulder, Philip J. R., Klenerman, Paul, Sewell, Andrew K., Easterbrook, Philippa J., Troop, Maxine, ...

Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate...

Copresentation of natural HIV-1 agonist and antagonist ligands fails to induce the T cell receptor signaling cascade

Purbhoo, Marco A., Sewell, Andrew K., Klenerman, Paul, Goulder, Philip J. R., Hilyard, Katherine L., Bell, John I., ...

It is not known how human immunodeficiency virus type 1 (HIV-1)-derived antagonist peptides interfere with intracellular activation of cytotoxic T lymphocytes (CTL). We identified Gag epitope...

An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses

André, Patrice, Groettrup, Marcus, Klenerman, Paul, De Giuli, Rita, Booth, Bruce L., Cerundolo, Vincenzo, ...

Inhibitors of the protease of HIV-1 have been used successfully for the treatment of HIV-1-infected patients and AIDS disease. We tested whether these protease inhibitory drugs exerted effects in...

Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection

Klenerman, Paul, Phillips, Rodney E., Rinaldo, Charles R., Wahl, Linda M., Ogg, Graham, May, Robert M., ...

To understand the role of the immune system in limiting HIV type 1 replication, it is critical to know to what extent the rapid turnover of productively infected cells is caused by viral...

Immune surveillance against a solid tumor fails because of immunological ignorance

Ochsenbein, Adrian F., Klenerman, Paul, Karrer, Urs, Ludewig, Burkhard, Pericin, Marcus, Hengartner, Hans, ...

Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, overall immune surveillance against...

Human CD1d–glycolipid tetramers generated by in vitro oxidative refolding chromatography

Karadimitris, Anastasios, Gadola, Stephan, Altamirano, Myriam, Brown, Dave, Woolfson, Adrian, Klenerman, Paul, ...

CD1 molecules are specialized in presenting lipids to T lymphocytes, but identification and isolation of CD1-restricted lipidspecific T cells has been hampered by the lack of reliable and sensitive...

CpG-Containing Oligonucleotides Are Efficient Adjuvants for Induction of Protective Antiviral Immune Responses with T-Cell Peptide Vaccines

Oxenius, Annette, Martinic, Marianne M. A., Hengartner, Hans, Klenerman, Paul

Synthetic nonmethylated oligonucleotides containing CpG dinucleotides (CpG-ODNs) have been shown to exhibit immunostimulatory activity. CpG-ODNs have the capacity to directly activate B cells,...

Additive Effect of Neutralizing Antibody and Antiviral Drug Treatment in Preventing Virus Escape and Persistence

Seiler, Peter, Senn, Beatrice M., Klenerman, Paul, Kalinke, Ulrich, Hengartner, Hans, Zinkernagel, Rolf M.

Poorly cytopathic or noncytopathic viruses can escape immune surveillance and establish a chronic infection. Here we exploited the strategy of combining antiviral drug treatment with the induction of...

Characterization of a Novel Respiratory Syncytial Virus-Specific Human Cytotoxic T-Lymphocyte Epitope

Goulder, Philip J. R., Lechner, Franziska, Klenerman, Paul, McIntosh, Kenneth, Walker, Bruce D.

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in childhood worldwide. The first human RSV-specific cytotoxic T-lymphocyte epitope to be defined is described. This HLA...

Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus

Gruener, Norbert H., Lechner, Franziska, Jung, Maria-Christina, Diepolder, Helmut, Gerlach, Tilman, Lauer, Georg, ...

Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences...

Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses

Lauer, Georg M., Nguyen, Tam N., Day, Cheryl L., Robbins, Gregory K., Flynn, Theresa, McGowan, Katherine, ...

Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently...

Effects of Promyelocytic Leukemia Protein on Virus-Host Balance

Bonilla, Weldy V., Pinschewer, Daniel D., Klenerman, Paul, Rousson, Valentin, Gaboli, Mirella, Pandolfi, Pier P., ...

The cellular promyelocytic leukemia protein (PML) associates with the proteins of several viruses and in some cases reduces viral propagation in cell culture. To examine the role of PML in vivo, we...

Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

Lauer, Georg M., Ouchi, Kei, Chung, Raymond T., Nguyen, Tam N., Day, Cheryl L., Purkis, Deborah R., ...

The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of...

Frequency and Phenotype of Circulating Vα24/Vβ11 Double-Positive Natural Killer T Cells during Hepatitis C Virus Infection

Lucas, Michaela, Gadola, Stephan, Meier, Ute, Young, Neil T., Harcourt, Gillian, Karadimitris, Anastasios, ...

Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Vα24/Vβ11 double positive, in hepatitis C virus (HCV)...

Boosting immunity by antiviral drug therapy: A simple relationship among timing, efficacy, and success

Komarova, Natalia L., Barnes, Eleanor, Klenerman, Paul, Wodarz, Dominik

Drug therapies against persistent human infections such as hepatitis C virus, hepatitis B virus, and HIV fail to consistently eradicate the infection from the host. Hence, recent emphasis has shifted...

Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers

Day, Cheryl L., Seth, Nilufer P., Lucas, Michaela, Appel, Heiner, Gauthier, Laurent, Lauer, Georg M., ...

Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells...

Expansion of Protective CD8+ T-Cell Responses Driven by Recombinant Cytomegaloviruses

Karrer, Urs, Wagner, Markus, Sierro, Sophie, Oxenius, Annette, Hengel, Hartmut, Dumrese, Tilman, ...

CD8+ T cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus, and cytomegalovirus (CMV). In most...

Underwhelming the Immune Response: Effect of Slow Virus Growth on CD8+-T-Lymphocyte Responses

Bocharov, Gennady, Ludewig, Burkhard, Bertoletti, Antonio, Klenerman, Paul, Junt, Tobias, Krebs, Philippe, ...

The speed of virus replication has typically been seen as an advantage for a virus in overcoming the ability of the immune system to control its population growth. Under some circumstances, the...

High-Resolution Phylogenetic Analysis of Hepatitis C Virus Adaptation and Its Relationship to Disease Progression

Sheridan, Isabelle, Pybus, Oliver G., Holmes, Edward C., Klenerman, Paul

Hepatitis C virus (HCV) persists in the majority of those infected despite host immune responses. Evidence has accrued that selectively fixed mutations in the envelope genes (E1 and E2) are...

Ex Vivo Phenotype and Frequency of Influenza Virus-Specific CD4 Memory T Cells

Lucas, Michaela, Day, Cheryl L., Wyer, Jessica R., Cunliffe, Sharon L., Loughry, Andrew, McMichael, Andrew J., ...

Recent advances in class II tetramer staining technology have allowed reliable direct ex vivo visualization of antigen-specific CD4 T cells. In order to define the frequency and phenotype of a...

Impact of Alpha Interferon and Ribavirin on the Function of Maturing Dendritic Cells

Barnes, Eleanor, Salio, Mariolina, Cerundolo, Vincenzo, Medlin, Joanne, Murphy, Shona, Dusheiko, Geoffrey, ...

Alpha interferon and ribavirin are required in combination to achieve a sustained virological response in the treatment of hepatitis C virus (HCV) infection. Alpha interferon has direct antiviral...

HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound

Scriba, Thomas J., Zhang, Hua-Tang, Brown, Helen L., Oxenius, Annette, Tamm, Norbert, Fidler, Sarah, ...

HIV-specific CD4+ T helper lymphocytes are preferred targets for infection. Although complete interruption of combination antiretroviral therapy (ART) can form part of therapeutic manipulations,...

Regulatory T Cells Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Persistent Hepatitis C Virus Infection

Rushbrook, Simon M., Ward, Scott M., Unitt, Esther, Vowler, Sarah L., Lucas, Michaela, Klenerman, Paul, ...

The basis of chronic infection following exposure to hepatitis C virus (HCV) infection is unexplained. One factor may be the low frequency and immature phenotype of virus-specific CD8+ T cells. The...

Shared Alterations in NK Cell Frequency, Phenotype, and Function in Chronic Human Immunodeficiency Virus and Hepatitis C Virus Infections

Meier, Ute-Christiane, Owen, Rachel E., Taylor, Elizabeth, Worth, Andrew, Naoumov, Nikolai, Willberg, Christian, ...

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause clinically important persistent infections. The effects of virus persistence on innate immunity, including NK cell responses, and...

Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection†

Pillay, Thillagavathie, Zhang, Hua-Tang, Drijfhout, Jan W., Robinson, Nicola, Brown, Helen, Khan, Munira, ...

The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant...

Sustained CD8+ T-Cell Responses Induced after Acute Parvovirus B19 Infection in Humans

Norbeck, Oscar, Isa, Adiba, Pöhlmann, Christoph, Broliden, Kristina, Kasprowicz, Victoria, Bowness, Paul, ...

Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally...

Full-Breadth Analysis of CD8+ T-Cell Responses in Acute Hepatitis C Virus Infection and Early Therapy

Lauer, Georg M., Lucas, Michaela, Timm, Joerg, Ouchi, Kei, Kim, Arthur Y., Day, Cheryl L., ...

Multispecific CD8+ T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of...

Prolonged Activation of Virus-Specific CD8+T Cells after Acute B19 Infection

Isa, Adiba, Kasprowicz, Victoria, Norbeck, Oscar, Loughry, Andrew, Jeffery, Katie, Broliden, Kristina, ...

Although parvovirus B19 apparently causes an acute viral infection, it appears to induce a persistent activated CD8 + T cell response.

Viral persistence in vivo through selection of neutralizing antibody-escape variants

Ciurea, Adrian, Klenerman, Paul, Hunziker, Lukas, Horvath, Edit, Senn, Beatrice M., Ochsenbein, Adrian F., ...

Despite initial virus control by CD8+ cytotoxic T lymphocytes (CTLs), noncytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HIV) are able to establish persistent infections....

A comparison of T cell memory against the same antigen induced by virus versus intracellular bacteria

Ochsenbein, Adrian F., Karrer, Urs, Klenerman, Paul, Althage, Alana, Ciurea, Adrian, Shen, Hao, ...

Cytotoxic T cell (CTL) memory was analyzed after infection with lymphocytic choriomeningitis virus (LCMV) and recombinant Listeria monocytogenes (rLM) expressing the complete nucleoprotein of LCMV...

Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice

Ciurea, Adrian, Klenerman, Paul, Hunziker, Lukas, Horvath, Edit, Odermatt, Bernhard, Ochsenbein, Adrian F., ...

Lymphocytic choriomeningitis virus (LCMV), strain WE, is a non-cytopathic RNA virus that is highly adapted to its natural host, the mouse. Acute infection of adult mice leads to generalized virus...

Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection

Price, David A., Goulder, Philip J. R., Klenerman, Paul, Sewell, Andrew K., Easterbrook, Philippa J., Troop, Maxine, ...

Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate...

Copresentation of natural HIV-1 agonist and antagonist ligands fails to induce the T cell receptor signaling cascade

Purbhoo, Marco A., Sewell, Andrew K., Klenerman, Paul, Goulder, Philip J. R., Hilyard, Katherine L., Bell, John I., ...

It is not known how human immunodeficiency virus type 1 (HIV-1)-derived antagonist peptides interfere with intracellular activation of cytotoxic T lymphocytes (CTL). We identified Gag epitope...

An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses

André, Patrice, Groettrup, Marcus, Klenerman, Paul, De Giuli, Rita, Booth, Bruce L., Cerundolo, Vincenzo, ...

Inhibitors of the protease of HIV-1 have been used successfully for the treatment of HIV-1-infected patients and AIDS disease. We tested whether these protease inhibitory drugs exerted effects in...

Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection

Klenerman, Paul, Phillips, Rodney E., Rinaldo, Charles R., Wahl, Linda M., Ogg, Graham, May, Robert M., ...

To understand the role of the immune system in limiting HIV type 1 replication, it is critical to know to what extent the rapid turnover of productively infected cells is caused by viral...

Immune surveillance against a solid tumor fails because of immunological ignorance

Ochsenbein, Adrian F., Klenerman, Paul, Karrer, Urs, Ludewig, Burkhard, Pericin, Marcus, Hengartner, Hans, ...

Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, overall immune surveillance against...

Human CD1d–glycolipid tetramers generated by in vitro oxidative refolding chromatography

Karadimitris, Anastasios, Gadola, Stephan, Altamirano, Myriam, Brown, Dave, Woolfson, Adrian, Klenerman, Paul, ...

CD1 molecules are specialized in presenting lipids to T lymphocytes, but identification and isolation of CD1-restricted lipidspecific T cells has been hampered by the lack of reliable and sensitive...

CpG-Containing Oligonucleotides Are Efficient Adjuvants for Induction of Protective Antiviral Immune Responses with T-Cell Peptide Vaccines

Oxenius, Annette, Martinic, Marianne M. A., Hengartner, Hans, Klenerman, Paul

Synthetic nonmethylated oligonucleotides containing CpG dinucleotides (CpG-ODNs) have been shown to exhibit immunostimulatory activity. CpG-ODNs have the capacity to directly activate B cells,...

Additive Effect of Neutralizing Antibody and Antiviral Drug Treatment in Preventing Virus Escape and Persistence

Seiler, Peter, Senn, Beatrice M., Klenerman, Paul, Kalinke, Ulrich, Hengartner, Hans, Zinkernagel, Rolf M.

Poorly cytopathic or noncytopathic viruses can escape immune surveillance and establish a chronic infection. Here we exploited the strategy of combining antiviral drug treatment with the induction of...

Characterization of a Novel Respiratory Syncytial Virus-Specific Human Cytotoxic T-Lymphocyte Epitope

Goulder, Philip J. R., Lechner, Franziska, Klenerman, Paul, McIntosh, Kenneth, Walker, Bruce D.

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in childhood worldwide. The first human RSV-specific cytotoxic T-lymphocyte epitope to be defined is described. This HLA...

Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus

Gruener, Norbert H., Lechner, Franziska, Jung, Maria-Christina, Diepolder, Helmut, Gerlach, Tilman, Lauer, Georg, ...

Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences...

Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses

Lauer, Georg M., Nguyen, Tam N., Day, Cheryl L., Robbins, Gregory K., Flynn, Theresa, McGowan, Katherine, ...

Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently...

Effects of Promyelocytic Leukemia Protein on Virus-Host Balance

Bonilla, Weldy V., Pinschewer, Daniel D., Klenerman, Paul, Rousson, Valentin, Gaboli, Mirella, Pandolfi, Pier P., ...

The cellular promyelocytic leukemia protein (PML) associates with the proteins of several viruses and in some cases reduces viral propagation in cell culture. To examine the role of PML in vivo, we...

Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

Lauer, Georg M., Ouchi, Kei, Chung, Raymond T., Nguyen, Tam N., Day, Cheryl L., Purkis, Deborah R., ...

The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of...

Frequency and Phenotype of Circulating Vα24/Vβ11 Double-Positive Natural Killer T Cells during Hepatitis C Virus Infection

Lucas, Michaela, Gadola, Stephan, Meier, Ute, Young, Neil T., Harcourt, Gillian, Karadimitris, Anastasios, ...

Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Vα24/Vβ11 double positive, in hepatitis C virus (HCV)...

Boosting immunity by antiviral drug therapy: A simple relationship among timing, efficacy, and success

Komarova, Natalia L., Barnes, Eleanor, Klenerman, Paul, Wodarz, Dominik

Drug therapies against persistent human infections such as hepatitis C virus, hepatitis B virus, and HIV fail to consistently eradicate the infection from the host. Hence, recent emphasis has shifted...

Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers

Day, Cheryl L., Seth, Nilufer P., Lucas, Michaela, Appel, Heiner, Gauthier, Laurent, Lauer, Georg M., ...

Containment of hepatitis C virus (HCV) and other chronic human viral infections is associated with persistence of virus-specific CD4 T cells, but ex vivo characterization of circulating CD4 T cells...

Expansion of Protective CD8+ T-Cell Responses Driven by Recombinant Cytomegaloviruses

Karrer, Urs, Wagner, Markus, Sierro, Sophie, Oxenius, Annette, Hengel, Hartmut, Dumrese, Tilman, ...

CD8+ T cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus, and cytomegalovirus (CMV). In most...