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You searched for +publisher:"University of KwaZulu-Natal" +contributor:("Goulder, Philip"). Showing records 1 – 2 of 2 total matches.

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University of KwaZulu-Natal

1. Moodley-Govender, Eshia S. Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity.

Degree: PhD, Paediatrics and child health, 2013, University of KwaZulu-Natal

Background: Prevention of Mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) remains a significant challenge in resource-poor settings despite the advances in antiretroviral (ARV) treatment. HIV-1 infected individuals are able to achieve viral control naturally, however the underlying mechanisms of immunological control in children remains poorly understood. This study was conducted from 2006 to 2010 to investigate correlates of immune control in HIV-1 clade C infected mother-child pairs in the absence of ARVs. Genotypic and phenotypic viral characteristics, cellular immune responses to HIV-1 and host genetics were characterized and correlated with clinical markers of disease progression. Materials and Methods: To achieve the objectives of the study, three cohorts of mother-child pairs were investigated. The first cohort included 60 untreated mother-child pairs and a further ten uninfected children as controls. The second cohort comprised of ARV treated pairs (n=60). The third cohort consisted of 374 mothers and 374 children (infected, exposed uninfected, HIV negative). Plasma viral loads and absolute CD4+ T cell counts were routinely performed in all three cohorts. HIV-specific CD8+ T cell responses were analyzed by interferon gamma (IFN-γ) enzyme linked immunosorbent spot (ELISpot) assays. Viral replicative fitness was assessed using a green fluorescent protein reporter cell line (GFP).Multi-parameter flowcytometry allowed for the investigation of T cell regulation, exhaustion and activation using CD127/CD25, TIM-3/PD-1 and HLA-DR/CD38 markers respectively. IL-10 promoter single nucleotide polymorphisms (SNPs) at positions -592 and -1082 were determined by TaqMan allelic discrimination assays. Plasma IL-10 levels were measured using a luminex assay. Results: To describe the CTL responses elicited to various regions of the HIV proteome in HIV-infected treatment naïve children. Sixty children under one year of age in the untreated cohort were analyzed for CTL responses spanning the HIV genome, for which only 30 had detectable responses. There was no significant difference in viral load between respondersand non-responders (p=0.2799). The responders predominantly targeted Nef (49%), Gag (17%) and Env (14%) regions. Markers of T cell exhaustion and regulation and theirrelationship to markers of disease progression, were next investigated as these parameters may explain the inability of T cells to effectively control HIV infection. T cell phenotyping compared treated, untreated and uninfected subgroups. In infected children, CD8+ T cells were significantly higher for both the inhibitory marker TIM-3 (p=0.001) and exhaustion marker PD-1 (p=0.0001) compared to uninfected children. Median expression of TIM-3 was higher on CD8+ T cells (46%) compared to CD4+ T cells (20%). TIM-3 and PD-1 expression on T cells were maintained at high levels over time. The frequency of absolute Tregs (p=0.0225) were found to be significantly higher in untreated compared to treated children. HLA-DR+CD38+ on CD8+ T… Advisors/Committee Members: Ndung'u, Thumbi (advisor), Addo, Marylyn (advisor), Goulder, Philip (advisor).

Subjects/Keywords: Paediatrics and child health.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Moodley-Govender, E. S. (2013). Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity. (Doctoral Dissertation). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/9871

Chicago Manual of Style (16th Edition):

Moodley-Govender, Eshia S. “Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity.” 2013. Doctoral Dissertation, University of KwaZulu-Natal. Accessed July 19, 2019. http://hdl.handle.net/10413/9871.

MLA Handbook (7th Edition):

Moodley-Govender, Eshia S. “Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity.” 2013. Web. 19 Jul 2019.

Vancouver:

Moodley-Govender ES. Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity. [Internet] [Doctoral dissertation]. University of KwaZulu-Natal; 2013. [cited 2019 Jul 19]. Available from: http://hdl.handle.net/10413/9871.

Council of Science Editors:

Moodley-Govender ES. Cellular immunity, immune activation and regulation in HIV-1 infected mother-child pairs : what are the determinants of protective immunity. [Doctoral Dissertation]. University of KwaZulu-Natal; 2013. Available from: http://hdl.handle.net/10413/9871


University of KwaZulu-Natal

2. Thobakgale, Christina Fanesa. HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).

Degree: PhD, Immunology, 2011, University of KwaZulu-Natal

The manifestation of HIV-1 infection is different in children and adults. Most of the children who acquire HIV perinatally progress to disease within the first two years of life, while adults can remain asymptomatic for up to ten years. However, a small minority group of children can control the virus for years in the absence of antiretroviral therapy. We characterized CD8+ T cell responses critical for the containment of HIV infection in a cohort of infants HIV infected from birth using IFN- γ ELISPOT, multicolour flow cytometry and viral sequencing of the Gag protein. We investigated whether the age at the time of infection, specificity and functionality of the generated responses, genetic make up and the maternal immune responses to HIV, influenced disease progression in the child. We found that the majority of in-utero infected infants mounted CD8+ T cell responses from the first days of life. In contrast to chronically infected children or adults, the specificity of the initial response in acutely infected infants was directed towards Env and Rev proteins and CD4+ T cell responses were minimal during the first 6 months of life. Slow progression to disease was associated with possession of one of the protective HLA-B alleles by either the mother or the child (P=0.007) and targeting of Gag epitopes presented by the protective HLA-B alleles. Mothers who expressed protective alleles but whose children did not possess these alleles, transmitted less fit viruses that benefited their children. Furthermore, slow progressor children had more polyfunctional CD8+ T cell responses in early infection when compared to rapid progressors (P=0.05). The ability of infants to induce CD8+ T cell responses early in life is encouraging for vaccine interventions. The differences in the specificity of the initial responses between adults and children, insufficient priming of these responses as a result of minimal CD4+ T cell help during infancy and possession of non-protective HLA alleles shared between mother and child, may explain the rapid disease progression generally noted in most infants. However, slow progression to disease in the minority group of children may be attributed to functional capacity of the CD8+ T cells generated by the child, mediation by protective HLA alleles, acquisition of low fitness viruses from the mother or de novo attenuation of the virus by the child’s own immune responses. Advisors/Committee Members: Kiepiela, Photini (advisor), Ndung'u, Thumbi (advisor), Goulder, Philip (advisor).

Subjects/Keywords: Immunology.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Thobakgale, C. F. (2011). HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI). (Doctoral Dissertation). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/5853

Chicago Manual of Style (16th Edition):

Thobakgale, Christina Fanesa. “HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).” 2011. Doctoral Dissertation, University of KwaZulu-Natal. Accessed July 19, 2019. http://hdl.handle.net/10413/5853.

MLA Handbook (7th Edition):

Thobakgale, Christina Fanesa. “HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).” 2011. Web. 19 Jul 2019.

Vancouver:

Thobakgale CF. HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI). [Internet] [Doctoral dissertation]. University of KwaZulu-Natal; 2011. [cited 2019 Jul 19]. Available from: http://hdl.handle.net/10413/5853.

Council of Science Editors:

Thobakgale CF. HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI). [Doctoral Dissertation]. University of KwaZulu-Natal; 2011. Available from: http://hdl.handle.net/10413/5853

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