CD28 costimulation and CD28 expression in T lymphocyte subsets in HIV-1 infection with and without progression to AIDS

In a prospective study of 152 HIV-1 patients (with and without progression to AIDS) we examined CD28 MoAb costimulation and CD3 MoAb response using wh ole blood culture at baseline and up to either the time of AIDS diagnosis o r the end of the observation period. CD28 antigen expression on both CD4(+) and CD8(+) T lymphocytes was also studied in both groups of patients. In p atients who progressed to AIDS, CD28 MoAb costimulation was found to be dec reased. Univariate time-dependent analysis showed that decreases in (i) abs olute numbers of either CD4(+), CD4(+)CD28(+), CD8(+)CD28(+) T cells, (ii) CD28 MoAb costimulation, and (iii) CD3 MoAb response, and an increase in CD 8(+)CD28(-) %, are significant predictors for progression to AIDS. In addit ion, multivariate time-dependent analysis demonstrated that a decrease in C D28 MoAb costimulation (but not a decrease in CD3 MoAb response) was predic tive for progression to AIDS, as were decreases in the percentage of CD4(+) T cells and the absolute number of CD4(+)CD28(+) T cells. Thus, CD28 MoAb costimulation can be considered a useful assay for monitoring HIV-1 infecti on. Furthermore, apart from the early increase in the percentage of CD8(+)C D28(-) T cells and an increase in the percentage of CD28(-) on CD8(+) T cel ls in both groups of patients at baseline compared with normal controls, a negative correlation was found to exist between the percentages of CD4(+) o r CD4(+)CD28(+) T cells and the percentage of CD8(+)CD28(-) T cells; this s uggests that these cells are probably mutually regulated.