HIV-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. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2011.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/8716 |
| Date | January 2011 |
| Creators | Ramduth, Dhanwanthie. |
| Contributors | Kiepiela, Photini., Ndung'u, Thumbi., Walker, Bruce D. |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
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