The expression of markers defining functional subpopulations on the surface of CD4 and CD8 cells changes with disease. To monitor these changes in children, it is important to establish the age-related normal changes in marker expression due to maturation of the immune system. We have studied the expression of several functionally important molecules on both CD4 and CD8 cells in 168 children (aged 0-122 months) using monoclonal antibodies and flow cytometry. Our results show that the percentage of CD4 cells decreases with age, while the CD8 percentage increases, resulting in a decrease in the CD4/CD8 ratio. The expression of CD45RO and CD29 increases with age, while CD45RA expression decreases, both on CD4 and CD8 cells. The expression of HLA-DR on both CD4 and CD8 cells, and of CD11a and CD57 on CD8 cells, is less clearly age dependent. The relationships between the marker percentages and age were not straightforward; the standard deviations and the skewness, as well as their mean values, varied as a function of age. The changes were modeled for each marker and age-specific centiles are presented.
SUMMARYThis study compares the predictive power of a single measurement of CD8 1 CD38 1 , CD81CD45RO 1 or CD8 1 CD38 1 CD45RO 1 subpopulations in predicting progression to AIDS in a cohort of HIV 1 longterm surviving injecting drug users. The results showed that both the total CD8 1 percentage, and the CD8 1 CD38 1 and CD8 1 CD38 1 CD45RO 1 subpopulations of cells all individually predicted progression to AIDS. In combination with CD4, only the CD8 1 CD38 1 subpopulation enhanced the predictive power of the CD4 percentage alone. The CD8 1 percentage correlated negatively with the CD4 percentage and the CD8 1 CD45RO 1 subpopulation did not predict disease progression. The proportion of CD8 1 CD38 1 cells identified which patients with a moderate CD4 level were more likely to progress to AIDS, and conversely, which patients with a low CD4 count were likely to remain clinically stable. The results were consistent irrespective of whether time was measured from the date of seroconversion, or from the date of the test. This study is the first to measure these markers in HIV-infected injecting drug users, and in long-term survivors. The results demonstrate the considerable added value of the CD8 1 CD38 1 cell percentage over the CD4 count alone, in predicting HIV clinical progression.
SUMMARYHIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CDS lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any. between CTL activity and CDS subpopuiations. We have measured CTL activity against four HIV gene products (gag. tat. pal and en\) and expression of CD45RO, CD45RA. HLA-DR, CD29. S6F1, and CD57 surface markers on CDS cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HW-gag. -pot and -tat. and the other to HW-pot. All the HIV-infected and two uninfected children had abnormal proportions of CDS subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CDS subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CDS cells, an expansion of HLA-DR^ CD8 cells and a loss of CD45RA ' CDS cells.
SUMMARYThe CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics ofthe CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1 + remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.
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