Publications
191 results found
Westrop SJ, Jackson A, Gazzard B, et al., 2011, HIV-1 clade A infection and viral control: an immunological perspective on a case of underquantification, INTERNATIONAL JOURNAL OF STD & AIDS, Vol: 22, Pages: 690-692, ISSN: 0956-4624
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- Citations: 3
Downey JS, Attaf M, Moyle G, et al., 2011, T-cell signalling in antiretroviral-treated, aviraemic HIV-1-positive individuals is present in a raised state of basal activation that contributes to T-cell hyporesponsiveness, AIDS, Vol: 25, Pages: 1981-1986, ISSN: 0269-9370
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- Citations: 3
Burton CT, Westrop SJ, Eccles-James I, et al., 2011, Altered phenotype of regulatory T cells associated with lack of human immunodeficiency virus (HIV)-1-specific suppressive function, Clinical and Experimental Immunology, Vol: 166, Pages: 191-200, ISSN: 0009-9104
Mechanisms by which CD4(+) regulatory T cells (T(regs) ) mediate suppression of virus-specific responses remain poorly defined. Adenosine, mediated via CD39 and CD73, has been shown to play a role in the action of murine T(regs) . In this study we investigate the phenotype of T(regs) in the context of human immunodeficiency virus (HIV)-1 infection, and the function of these cells in response to HIV-1-Gag and cytomegalovirus (CMV) peptides. Phenotypic data demonstrate a decrease in forkhead box transcription factor 3 (FoxP3(+) ) T(reg) numbers in the peripheral blood of HIV-1(+) individuals compared to healthy controls, which is most pronounced in those with high HIV-1 RNA plasma load. Due to aberrant expression of CD27 and CD127 during HIV-1 disease, these markers are unreliable for T(reg) identification. The CD3(+) CD4(+) CD25(hi) CD45RO(+) phenotype correlated well with FoxP3 expression in both the HIV-1(+) and seronegative control cohorts. We observed expression of CD39 but not CD73 on T(regs) from HIV-1(+) and healthy control cohorts. We demonstrate, through T(reg) depletion, the suppressive potential of T(regs) over anti-CMV responses in the context of HIV-1 infection; however, no recovery of the HIV-1-specific T cell response was observed indicating a preferential loss of HIV-1-specific T(reg) function. We propose that before immunotherapeutic manipulation of T(regs) is considered, the immunoregulatory profile and distribution kinetics of this population in chronic HIV-1 infection must be elucidated fully.
Gudmundsdotter L, Wahren B, Haller BK, et al., 2011, Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial, VACCINE, Vol: 29, Pages: 5558-5566, ISSN: 0264-410X
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- Citations: 25
Grageda N, Westrop S, Gazzard B, et al., 2011, Novel technology for HLA-B*3501 epitope prediction and kinetics within the HIV-1 capsid Gag, Publisher: WILEY-BLACKWELL, Pages: 28-28, ISSN: 1464-2662
Westrop S, D'Souza G, Bower M, et al., 2011, Algorithmic prediction for the identification of novel HLA-B*2705-restricted HIV-1 CD8 T-cell epitopes: assessment of epitope stability, affinity and specific T-cell profile, Publisher: WILEY-BLACKWELL, Pages: 29-29, ISSN: 1464-2662
Herasimtschuk A, Downey J, Nelson M, et al., 2011, Impact of IL-2/GM-CSF, rhGH and therapeutic immunization in treated HIV-1 infection: a randomized, open-label, Phase I immunotherapeutic study, HIV MEDICINE, Vol: 12, Pages: 27-27, ISSN: 1464-2662
Begom S, Coleman A, Gazzard B, et al., 2011, Gamma-delta T cell responsiveness to zoledronic acid and adjuvant potential in HIV-1 infection, HIV MEDICINE, Vol: 12, Pages: 26-26, ISSN: 1464-2662
Coleman A, Imami N, Gazzard B, et al., 2011, Enhancement of HIV-1 gag-specific T cell responses by type A CpG DNA, HIV MEDICINE, Vol: 12, Pages: 25-26, ISSN: 1464-2662
Mandalia S, Westrop S, Beck E, et al., 2011, Frequency and characteristics of long-term non-progressors and HIV controllers in the Chelsea and Westminster HIV cohort, Publisher: WILEY-BLACKWELL, Pages: 10-11, ISSN: 1464-2662
Westrop S, Lagos D, Bower M, et al., 2011, Increased incidence of multicentric Castleman's disease in KSHV<SUP>+</SUP> HIV-1<SUP>+</SUP> individuals of Black African ethnicity may result from the higher frequency of the TLR4 single nucleotide polymorphism A299G, Publisher: WILEY-BLACKWELL, Pages: 6-7, ISSN: 1464-2662
Herasimtschuk A, Downey J, Nelson M, et al., 2011, Impact of IL-2/GM-CSF, rhGH and therapeutic immunization in treated HIV-1 infection: a randomized, open-label, Phase I immunotherapeutic study, 17th Annual Conference of the British HIV Association (BHIVA)
Coleman A, Imami N, Gazzard B, et al., 2011, Enhancement of HIV-1 Gag-specific T cell responses by type A CpG DNA, 17th Annual Conference of the British HIV Association (BHIVA)
Westrop SJ, Lagos D, Bower M, et al., 2011, Increased incidence of multicentric Castleman’s disease in KSHV+ HIV-1+ individuals of Black African ethnicity may result from the higher frequency of the TLR4 single nucleotide polymorphism A299G, 17th Annual Conference of the British HIV Association
Mandalia S, Westrop SJ, Beck E, et al., 2011, Frequency and characteristics of long-termnon-progressors and HIV controllers in the Chelsea andWestminster HIV cohort, 17th Annual Conference of the British HIV Association
Westrop SJ, D'Souza G, Bower M, et al., 2011, Algorithmic prediction for the identification of novel HLA-B*2705-restricted HIV-1 CD8 T-cell epitopes: assessment of epitope stability, affinity and specific T-cell profile, 17th Annual Conference of the British HIV Association
Gotch F, Downey J, Herasimtschuk A, et al., 2010, Can novel rational immunotherapy lead to long term non-progressor status in chronically infected HIV plus persons receiving antiretroviral therapy (ART)?, AIDS Vaccine 2010, Publisher: MARY ANN LIEBERT INC, Pages: A89-A89, ISSN: 0889-2229
Westrop SJ, Moyle GJ, Imami N, 2010, Nature and Function of CCR5 in Immune Activation, HIV-1 Entry, and Targeted Therapeutics, The Journal of Viral Entry, Vol: 4, Pages: 1-10
Downey JS, Imami N, 2010, T-cell dysfunction in HIV-1 infection: targeting the inhibitors, HIV Therapy, Vol: 4, Pages: 83-99, ISSN: 1758-4310
<jats:p>Since AIDS emerged almost three decades ago, there have been considerable advances in the field of antiretroviral chemotherapy for those chronically infected with HIV-1. However, this therapy is noncurative and as our understanding of HIV-1 immunopathogenesis increases, it is becoming apparent that further therapeutic interventions are required to reverse the devastating effects of HIV-1 infection worldwide. While viral clearance remains the principle goal of HIV-1 treatment, this article describes immunotherapeutic options that target the immunological effects of the virus, to reduce its presence in the body and counteract viral-induced T-cell dysfunction and inhibition. Such approaches may augment existing antiretroviral therapy to overturn virus-induced T-cell anergy in the infected host, improving levels of immune control that reduce viremia and decrease the rate of transmission.</jats:p>
Rosignoli G, Lim CH, Bower M, et al., 2009, Programmed death (PD)-1 molecule and its ligand PD-L1 distribution among memory CD4 and CD8 T cell subsets in human immunodeficiency virus-1-infected individuals, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 157, Pages: 90-97, ISSN: 0009-9104
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- Citations: 38
Westrop SJ, Qazi NA, Pido-Lopez J, et al., 2009, Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers, PLOS One, Vol: 4, ISSN: 1932-6203
BackgroundHIV-1+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.Methodology/Principal FindingsCD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-γ ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1+ individuals originally identified as “Long-term non-progressors” in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-γ producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-γ production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-γ production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.ConclusionsAlthough increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory
Heltai S, Malnati MS, Cosma A, et al., 2009, A NEW ANTIGEN-SCANNING STRATEGY TO MONITOR T-CELL IMMUNE RESPONSES, Publisher: URBAN & VOGEL, Pages: 86-86, ISSN: 0300-8126
Westrop SJ, Pido-Lopez J, Grageda N, et al., 2009, The role of CD8+T cell-mediated immunity in HIV-1 disease progression: rapid, chronic and controlled, HIV MEDICINE, Vol: 10, Pages: 43-44, ISSN: 1464-2662
Westrop SJ, Jackson A, Nelson M, et al., 2009, HIV-1 clade A infection and viral control: An immunological perspective on a case of under-quantification, HIV MEDICINE, Vol: 10, Pages: 43-43, ISSN: 1464-2662
Herasimtschuk A, Nelson M, Moyle G, et al., 2009, Impact of recombinant human growth hormone on T-cell phenotype and function <i>in vitro</i> and <i>in vivo</i> during treated HIV-1 infection, HIV MEDICINE, Vol: 10, Pages: 5-6, ISSN: 1464-2662
Westrop SJ, Grageda N, Imami N, 2009, Novel approach to recognition of predicted HIV-1 Gag B*3501-restricted CD8 T-cell epitopes by HLA-B*3501<SUP>+</SUP> patients: Confirmation by quantitative ELISpot analyses and characterisation using multimers, JOURNAL OF IMMUNOLOGICAL METHODS, Vol: 341, Pages: 76-85, ISSN: 0022-1759
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- Citations: 10
Kyosiimire-Lugemwa J, Pala P, Miiro G, et al., 2009, P16-16. Gag and Nef specific T-cell responses in HIV-1 infected long-term non-progressors in Uganda, Retrovirology, Vol: 6, Pages: P245-P245, ISSN: 1742-4690
Kyosiimire-Lugemwa J, Pala P, Miiro G, et al., 2009, Gag and Nef specific T-cell responses in HIV-1 infected long-term non-progressors in Uganda, RETROVIROLOGY, Vol: 6, ISSN: 1742-4690
Westrop SJ, Mandalla S, Nelson M, et al., 2009, Evaluation of CD8<SUP>+</SUP> T-Cell-Mediated Selection Pressure on Proviral Gag p17 and p24 in Chronically Infected HIV-1<SUP>+</SUP> Individuals, 2nd European Congress of Immunology (ECI), Publisher: MEDIMOND S R L, Pages: 171-+
Westrop SJ, Grageda N, Imami N, 2009, Novel Approach to Recognition of Predicted HIV-1 Gag B*3501-Restricted CD8 T-Cell Epitopes by HLA-B*3501*Patients: Confirmation by Quantitative ELISpot Analyses and Characterisation Using Multimers, 2nd European Congress of Immunology (ECI), Publisher: MEDIMOND S R L, Pages: 429-433
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