| Summary: | Infection with Human Immunodeficiency Virus, type 1 (HIV-1) is associated with a gradual progressive decline in the number of CD4+ T lymphocytes. Effective treatment suppresses viral replication and is accompanied by a concomitant increase in the number of CD4+ T cells. Immune reconstitution of CD4+ T cells in children following treatment is characterised by a sustained increase of naïve cells, a pattern that differs from that seen in adults. The aim of this thesis was to explore how these changes occur. CD4+ T cells in blood samples from HIV-1 infected children were identified, divided into sub-populations and analysed for apoptosis, proliferation, activation and differentiation by flow cytometry. Four CD4+ T cell sub-populations, with varying contributions to the total CD4+ T cell pool were thus identified: (i) recent thymic emigrants (RTEs) made up the largest population yet maintained very low levels of proliferation despite increased viral replication and cellular activation, and were consistently greater in children with undetectable viraemia; (ii) central naïve cells, which were fairly constant in HIV-1 infected children of all ages regardless of CD4 count; (iii) CD31- memory cells that increased as CD4 count fell and (iv) CD31+ memory cells that despite their high level of activation and proliferation remained a small population across age, viral load and CD4 count. Treatment interruption and the resulting increased viraemia and decreased CD4 count were associated with only transient changes to the percentage contribution of each subset, which supports the existence of a setpoint for each subpopulation. This thesis infers the importance of thymic output in maintaining the CD4 count and hence the potential for using RTEs in monitoring response to treatment and sheds light on the role and origin of CD31+ memory cells as a small but highly activated population that may be important in disease pathogenesis.
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