| Summary: | This thesis describes the cytotoxic T lymphocyte (CTL) responses in a cohort of HIV-infected (HIV+ve) children, in relation to their clinical disease progression. CTL responses are thought to be one of the major mechanisms by which primary HIV-viraemia is cleared and clinical stability maintained. CTL activity was measured against four HIV gene products (gag, tat, pol, env). Three patterns of CTL activity were seen in the HIV+ve children: (i) CTL activity against HIV-pol, -gag and/or -env; (ii) CTL activity against HIV-tat and/or -pol; (iii) No CTL activity detected. These different patterns appear to relate to different patterns of clinical disease progression. CTL activity was also detected in HIV-ve (but exposed) children, but the specificity was predominantly to HIV-env. Stimulation of PBMCs with peptides of specific CTL epitopes of HIV resulted in a change in specificity of CTL recognition. These data suggest that the specificity of the CTL response may be related to clinical progression of the child, and that different CTL responses are obtained by different methods of stimulation of PBMCs. Changes in lymphocyte surface marker expression in peripheral blood were investigated to see if any phenotype was related to CTL activity, or was indicative of the infection status of the child, or disease progression. Activated, memory, CD8+ T cell populations were markedly increased soon after birth in HIV+ve children and remained so throughout infection. An increase in the proportion of the activated or memory CD4+ T cells may indicate an imminent and accelerated CD4+ cell loss, and subsequent progression to AIDS. The results indicate that the HIV+ve children showed anti-HIV responses through different mechanisms. It is possible that these may contribute to the immunopathogenic effects seen in HIV infection and affect the clinical patterns of disease progression in individual children.
|
|---|
