Capacity of toxitoxic T lymphocytes to control the reproduction of human immunodeficiency virus

The focus of the work presented in this thesis is on CTL directed against HIV-1. Chapter 2 addresses frequencies of circulating CTL, their specificity at the protein and epitope level, and associations of CTL responses with rapid or slow disease progression in HIV -1 infection. Studies on the capacity of CTL to control reproduction of HIV are presented in chapter 3. Together, the data presented in chapters 2 and 3 support the concept that CTL directed against the early regulatory proteins Rev and Tat are more effective in controlling HIV reproduction than CTL directed against the late structural proteins Gag and RT. The main hypothesis addressed in this thesis is that CTL control reproduction of HIV more effectively if they are able to recognize infected cells earlier after the entry of virus. This would enable CTL to eliminate more infected cells before release of infectious progeny virus begins, and thus to prevent more subsequent infection cycles. This hypothesis was also tested in vivo by comparing the ability of cynomolgus macaques to control an experimental SIV infection after being vaccinated with Rev and Tat or with Gag and RT. The results of these studies are in described in chapter 4. Chapter 5 discusses the findings presented in this thesis and their significance for AIDS vaccine development. A summary is provided in chapter 6.

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