Aileen Rowan

Aileen Rowan
Imperial College London | Imperial · Division of Infectious Diseases

Doctor of Philosophy

About

76
Publications
3,588
Reads
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1,198
Citations
Citations since 2017
17 Research Items
629 Citations
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2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
Introduction
Dr Aileen Rowan is a human immunologist specialized in chronic viral infection and cancer. She studies the mechanisms by which the retrovirus Human T cell lymphotropic virus-1 (HTLV-1) causes persistent infection and cancer in humans, with particular focus on interactions between ex vivo naturally infected cells and autologous, in vivo primed, virus-specific T cells. Aileen is currently conducting translational research in the National Centre for Human Retrovirology at Imperial College London, where she is investigating the genomic changes which occur in the late stages of HTLV-1 oncogenesis, and developing assays of T cell diversity for early detection of T cell malignancies.
Skills and Expertise
Additional affiliations
May 2008 - present
Imperial College London
Position
  • Research Associate
September 2003 - October 2007
Trinity College Dublin
Position
  • PhD Student

Publications

Publications (76)
Article
Full-text available
There is growing evidence that CD8⁺ cytotoxic T lymphocyte (CTL) responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1), contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-produc...
Article
Full-text available
Human T cell lymphotropic virus-1 (HTLV-1) primarily infects CD4+ T cells, causing inflammatory disorders or a T cell malignancy in 5% to 10% of carriers. The cytotoxic T lymphocyte (CTL) response is a key factor that controls the viral load and thus the risk of disease. The ability to detect the viral protein Tax in primary cells has made it possi...
Article
Full-text available
Human T lymphotropic virus type 1 (HTLV-1) appears to persist in the chronic phase of infection by driving oligoclonal proliferation of infected T cells. Our recent high-throughput sequencing study revealed a large number (often > 10(4)) of distinct proviral integration sites of HTLV-1 in each host that is greatly in excess of previous estimates. H...
Article
Full-text available
CD8(+) T cells can exert both protective and harmful effects on the virus-infected host. However, there is no systematic method to identify the attributes of a protective CD8(+) T cell response. Here, we combine theory and experiment to identify and quantify the contribution of all HLA class I alleles to host protection against infection with a giv...
Article
Full-text available
In human T-lymphotropic virus type 1 (HTLV-1) infection, a high frequency of HTLV-1-specific CTLs can co-exist stably with a high proviral load and the proviral load is strongly correlated with the risk of HTLV-1-associated inflammatory diseases. These observations led to the hypothesis that HTLV-1 specific CTLs are ineffective in controlling HTLV-...
Article
There is growing evidence that measurement of SARS-CoV-2 viral copy number can inform clinical and public health management of SARS-CoV-2 carriers and COVID-19 patients. Here we show that quantification of SARS-CoV-2 is feasible in a clinical setting, using a duplex RT-qPCR assay which targets both the E gene (Charité assay) and a human RNA transcr...
Article
Background Coinfection with HIV-1 and HTLV-1 diminishes the value of the CD4 + T-cell count in diagnosing AIDS, and increases the rate of HTLV-1-associated myelopathy. It remains elusive how HIV-1/HTLV-1 coinfection is related to such clinical characteristics. Here, we investigated the mutual effect of HIV-1/HTLV-1 coinfection on their integration...
Article
Full-text available
Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26− T-cells) using an ‘olig...
Preprint
Full-text available
Background. Transmission of SARS-CoV-2 by children and young people in school settings has not been directly evaluated, nor the main mechanisms of transmission identified. The study set out to undertake sequential longitudinal sampling of infected children, their contacts, and the environment. Methods. Cases of COVID-19 were identified through stat...
Article
Full-text available
Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of...
Article
Full-text available
Background: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) is an inflammatory condition characterized by severe disability and high levels of infected white blood cells. The circulating cellular inflammatory changes that distinguish this condition from asymptomatic infection are not well understood. Methods: To investigat...
Article
Full-text available
Adult T cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by Human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targ...
Article
Full-text available
Human T-cell leukemia virus type 1 (HTLV-1) has infected as many as 10 million people worldwide. While 90% are asymptomatic, 5% develop severe diseases including adult T-cell leukemia/lymphoka (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). No vaccine against HTLV-1 exists, and screening programs are not universal. H...
Article
Full-text available
The prognosis of adult T-cell leukemia-lymphoma (ATL) remains very poor, and there is an urgent clinical need to investigate novel therapies for ATL. The expression of phosphatidylinositol 3-kinase-δ (PI3k-δ) is normally restricted to hematopoietic cells and is known as a key determinant of cell survival in certain cancers. The inhibitor of PI3k-δ,...
Article
Globally, > 5–10 million people are estimated to be infected with Human T-lymphotropic virus type 1 (HTLV-1), of whom ~ 5% develop adult T-cell leukemia/lymphoma (ATL). Despite advances in chemotherapy, overall survival (OS) has not improved in the 35 years since HTLV-1 was first described. In Europe/USA, combination treatment with zidovudine and i...
Article
Background: Adult T-cell leukaemia/lymphoma (ATL) is an aggressive T-cell malignancy caused by HTLV-1 infection. Typically patients treated with chemotherapy show transient remissions followed by early relapse. There is a need for markers that can predict the response to therapy early in treatment in order to stratify patients who should be conside...
Data
PD-L1 and FoxP3 expression. (TIF)
Data
Killing of ATL cells and non-malignant infected cells is inhibited in the presence of 20 nM Concanamycin A. (TIF)
Data
Frequency of TCRVβ subsets. (A) Frequency of CD4+TCRVβ+ populations as a percentage of total live CD3+ cells. (B) Size of largest possible clone by ATL subtype. (TIF)
Data
Normal range of maximum clone frequency in non-malignant HTLV-1 infected donors. (TIF)
Data
Example staining for HLA-ABC, Tax, FoxP3 and PD-L1. (TIF)
Data
Gating strategy for TCRVβ flow cytometric analysis. (TIF)
Data
High frequencies of CCR4+CADM1+CD7− cells in donors with ATL. (TIF)
Data
Gating strategy used in cell survival assay. (A) Gating strategy used for multiparameter analysis (B) Gating strategy for absolute T cell counts. (TIF)
Chapter
Human T lymphotropic virus 1 (HTLV-1) was discovered in 1980, when Robert Gallo and his colleagues observed production of retroviral particles by a cell line established from a patient with a T-cell lymphoma (Poiesz et al. 1980). Concurrently, two groups in Jamaica and Japan detected HTLV-1-specific antibodies in the cerebrospinal fluid (CSF) and s...
Data
CD25, CCR4 and ICAM-1 expression on uncultured CD4+ cells. (A) The median frequency of cells in each group of patients. (B) PVL versus frequency of cells in each subset. (TIF)
Data
Kinetics and intensity of Tax expression in CADM1+/–CD4+ T cells. (A) Frequency of live CD3+CD4+ cells expressing Tax. (B) Intensity of Tax expression by live CAMD1+/–CD3+CD4+ cells (TIF)
Data
CD25, CCR4 and ICAM-1 expression on uncultured CD8+ cells. (TIF)
Data
Median PVL and proportion of cells expressing Tax in CD4+ cells sorted on the basis of CADM1, CCR4 and CD25 expression. (A) Sorting strategy. (B) PVL of total CD4+ T cells and sorted populations. (C) The proportion of load carried by CADM1 or Tax expressing CD4+ cells. (TIF)
Data
Flow cytometric gating strategy for cell surface analysis. (TIF)
Data
Flow cytometric gating strategy for cell sorting experiments. (TIF)
Data
Sensitivity and specificity with which each surface marker detects Tax expressing cells. (TIF)
Data
CD25+CADM1+ cells are more likely to express Tax than CD25–CADM1+ cells. (A) Representative dot plot. (B) The proportion of CADM1+CD25+ and CADM1+CD25– cells that express Tax after 16h culture. (TIF)
Data
Distribution of proviral load in PBMC. (A) Copies of HTLV-1 per cell for each individual. (B) Frequency of T cell subsets in PBMC. (C) Proportion of load carried in CADM1+ lymphocytes versus proviral load in PBMC. (TIF)
Article
Full-text available
Background Human T-lymphotropic Virus Type I (HTLV-1) is a retrovirus that persistently infects 5–10 million individuals worldwide and causes disabling or fatal inflammatory and malignant diseases. The majority of the HTLV-1 proviral load is found in CD4+ T cells, and the phenotype of adult T cell leukemia (ATL) is typically CD4+. HTLV-1 also infec...
Article
Full-text available
Adult T cell leukaemia/lymphoma (ATL) is a predominantly CD4+ T cell neoplasia caused by human T cell lymphotropic Virus 1 (HTLV-1) infection. A few cases of CD8+ ATL have been reported but its existence has been debated. An Afrocaribbean female presented to the dermatology clinic with widespread papulo-nodular rash. HTLV-1 infection was detected b...
Article
Full-text available
HTLV-1 Tax protein is usually undetectable in freshly isolated peripheral blood mononuclear cells (PBMCs). After in vitro culture, the provirus is reactivated and Tax protein is detectable only in a proportion of infected CD4+ T cells: the percentage of Tax+ cells is always lower than the proviral load (PVL). To identify and further analyse the lat...
Article
Full-text available
Adult T cell leukaemia/lymphoma (ATL) is a highly heterogeneous neoplasm caused by human T cell lymphotropic virus type 1 (HTLV-1) infection. Shimoyama et al first proposed a prognostic classification based on clinical features. However subsequent studies have highlighted even greater heterogeneity and progression from indolent to aggressive subtyp...
Article
Full-text available
The integration of Human T-lymphotropic virus type I (HTLV-1) is known to be diverse but biased towards geno-mically active regions. Each infected clone is identified by a unique integration site position. The integration site position is known to be associated with the expression pattern of the provirus and its propensity to expand in vivo but it...
Conference Paper
Full-text available
Significance The retrovirus human T-lymphotropic virus type 1 (HTLV-1) causes inflammatory and malignant diseases in humans. To maintain latency and avoid immune detection in vivo, HTLV-1 minimizes expression of genes on the plus-strand of the integrated provirus but allows constitutive expression of the minus-strand gene, which maintains clonal pe...
Conference Paper
Full-text available
Adult T cell leukemia (ATL) is typically characterised by expansion of a single dominant malignantly transformed HTLV-1-infected clone. Clinically, the abundance of this clone can be estimated by flow cytometric assessment of CD4, CD25 and CD7 expression, and, more recently, by quantitative LM-PCR analysis of viral integration site. In addition to...
Conference Paper
Full-text available
Human T-lymphotropic virus type I (HTLV-1) integration is known to be weakly biased towards genomically active regions but can occur throughout the genome. We have shown that there are of the order of 10^4 HTLV-1-infected T-cell clones in each individual, each clone defined by a unique genomic integration site of the single-copy HTLV-1 provirus. HT...
Article
Full-text available
Background Immunogenetic evidence indicates that cytotoxic T lymphocytes (CTLs) specific for the weak CTL antigen HBZ limit HTLV-1 proviral load in vivo, whereas there is no clear relationship between the proviral load and the frequency of CTLs specific for the immunodominant antigen Tax. In vivo, circulating HTLV-1-infected cells express HBZ mRNA...
Article
Full-text available
Human T-lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) both cause lifelong persistent infections, but differ in their clinical outcomes. HTLV-1 infection causes a chronic or acute T-lymphocytic malignancy in up to 5% of infected individuals whereas HTLV-2 has not been unequivocally linked to a T-cell malignancy. Virus-driven clonal prolifer...
Article
Full-text available
Host cytotoxic T-lymphocyte (CTL) responses are critical in limiting expansion of HTLV-1-infected CD4+T-cells in vivo, and most individuals generate abundant Tax-specific CTL. Although Tax is immunodominant, the ability to efficiently present peptides from HBZ on MHC class 1 is associated with a lower proviral load and a reduced frequency of HAM/TS...
Article
Full-text available
An efficient antiviral cytotoxic T lymphocyte (CTL) response to HTLV-1 infection maintains a low proviral load (PVL), reducing the risk of HAM/TSP. Host genotype , particularly of HLA class I, is a major determinant of CTL efficiency, and the influence of specific HLA class I alleles on HTLV-1 immunity is well documented. We recently showed that ki...
Article
Table 1. HLA class I binding of peptides from different HTLV-1 proteins has a differential impact on both proviral load and HAM/TSP risk. Left hand column: The HTLV-1 proteins were ranked according to whether they targeting them was associated with asymptomatic status. This list could be viewed as the “rank order of targets for a vaccine designed t...
Article
Full-text available
ATLL is an aggressive malignancy of T cells that affects about 5% of individuals infected with HTLV-1. The precise mechanism of oncogenesis is not known, but there is evidence that two regulatory viral proteins, Tax and HBZ, are involved. A high set point proviral load is associated with development of ATLL or a chronic inflammatory condition, HAM/...
Article
Full-text available
In search of novel biomarkers of HTLV-1-transformed cells with relevance to oncogenesis, we identified the tumour marker and actin-bundling protein Fascin (FSCN1) to be specifically and strongly upregulated in both HTLV-1-transformed and ATLL-patient-derived CD4+ T cells. Fascin is important for migration and metastasis in various types of cancer....
Article
Full-text available
Host cytotoxic lymphocyte (CTL) responses play an essential role in limiting clonal expansion of infected CD4+ T cells in HTLV-1+ individuals. We have reported that individuals who possess HLA class 1 alleles that strongly bind peptides from HTLV-1 basic leucine zipper protein (HBZ) have a lower proviral load and are less likely to develop HAM/TSP....
Article
Full-text available
HTLV-1 propagates in the host by two parallel mechanisms: infectious spread, i.e. direct transfer of virions from cell to cell via the virological synapse; and mitotic spread, i.e. proliferation of HTLV-1-infected T cell clones. During chronic infection, mitotic spread predominates , generating very large clones in some individuals. Yet the reasons...
Article
Full-text available
The roles of the human T-lymphotropic virus type 1 (HTLV-1) basic leucine zipper (HBZ) gene are not clearly understood. We examined CD8+ and CD4+ T cell responses to HBZ and compared these with Tax responses. Interferon (IFN)-γ and interleukin (IL)-2-secreting T cells were detected by enzyme-linked immunosorbent spot (ELISpot) assays of freshly iso...
Article
Full-text available
Oncogenic transformation of CD4(+) T cells by human T-cell lymphotropic virus type 1 (HTLV-1) is understood as the initial step to adult T-cell leukemia/lymphoma, a process that is mainly initiated by perturbation of cellular signaling by the viral Tax oncoprotein, a potent transcriptional regulator. In search of novel biomarkers with relevance to...
Article
Full-text available
IL-17-secreting T (Th17) cells play a protective role in certain bacterial infections, but they are major mediators of inflammation and are pathogenic in organ-specific autoimmune diseases. However, human Th17 cells appear to be resistant to suppression by CD4(+)CD25(+)FoxP3(+) regulatory T cells, suggesting that they may be regulated by alternativ...
Article
Protective immunity against viruses, bacteria, parasites and fungi is mediated by innate and adaptive immune responses of the hosts. However, pathogens have developed strategies for subverting these responses and thereby establishing persistent or chronic infections. Furthermore, anti-pathogen effector immune responses must be tightly regulated to...
Article
The majority of hepatitis C virus (HCV) infections become chronic, despite the presence of HCV-specific cellular and humoral immune responses. We have previously suggested that IL-10-secreting antigen-specific regulatory T cells may contribute to viral persistence, and demonstrate here that peripheral blood mononuclear cells (PBMC) from chronically...

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