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Characterization of CD4+ and CD8+ T cell responses in HIV-1 C-Clade infection.

dc.contributor.advisorKiepiela, Photini.
dc.contributor.advisorNdung'u, Peter Thumbi.
dc.contributor.advisorWalker, Bruce D.
dc.contributor.authorRamduth, Dhanwanthie.
dc.date.accessioned2013-03-19T07:46:50Z
dc.date.available2013-03-19T07:46:50Z
dc.date.created2011
dc.date.issued2011
dc.descriptionThesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.en
dc.description.abstractHIV-1 specific CD4+ T cell activity in clade C infected subjects has not been studied. CD4+ T cells play a vital role in controlling infectious diseases and there is a need to augment our knowledge of HIV immunology to aid vaccine design. We therefore embarked on a study to characterize HIV-1 specific CD4+ T cell activity in both adults and infants; assess the relationship between CD4+ and CD8+ immune responses; and the relationship between CD4+ T cell activity and markers of disease progression (viral loads and CD4 counts). Our study revealed that the magnitude of CD8+ T cell responses correlated significantly with CD4+ T cell responses, but that the percentage of CD8+ T cells directed against HIV-1 was always greater than that of CD4+ T cells. Gag was the frequently targeted HIV-1 protein by CD4+ T cells and had the highest density of epitopes targeted by CD4+ T cells. Patients with either a dominant CD4 or CD8 T cell response against Gag had significantly lower viral loads than patients in whom non-Gag proteins were the main target (p< 0.0001 for CD4 activity and p= 0.007 for CD8 responses). Single IFN- producing CD4+ T cells were present in significantly higher numbers than cells producing both IFN- and IL-2 simultaneously (p=0.009). Gag also dominated the CD4+ T cell response in acutely infected infants with IFN- production detected more frequently than IL-2 or TNF- . Longitudinal analysis of infants receiving early ARV treatment and then ceasing after 12 months revealed that early treatment conferred no protection against increasing viremia and disease progression. CD4+ T cell responses were detected sporadically in untreated infants indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia. Taken together, the data reveal that a vaccine inducing Gag specific CD4+ T cell responses has the potential to confer some degree of protection, but other immunological parameters need to be investigated especially in infants.en
dc.identifier.urihttp://hdl.handle.net/10413/8716
dc.language.isoen_ZAen
dc.subjectHIV-positive children--KwaZulu-Natal.en
dc.subjectImmunologic diseases in infants--KwaZulu-Natal.en
dc.subjectAIDS (Disease) in infants--KwaZulu-Natalen
dc.subjectHuman immunogenetics--KwaZulu-Natal.en
dc.subjectT cells.en
dc.subjectTheses--Immunology.en
dc.titleCharacterization of CD4+ and CD8+ T cell responses in HIV-1 C-Clade infection.en
dc.typeThesisen

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