Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: Correlation with decreased CD28 expression

In 219 HIV-1-infected men of the Amsterdam cohort we measured CD4(+) T cell numbers and in vitro T cell responses to CD3 MoAbs with or without CD28 costimulation and phytohaemagglutinin (PHA). The value of these markers was estimated for disease progression within 4 years. CD28 expression on T cells has been related to T cell responses. CD28 costimulation considerably enhanced T cell reactivity (approximate to 8-10-fold) with lower coefficients of variation compared with reactivity to CD3 MoAb alone (median 5 versus 20). T cell reactivity to CD3 plus CD28 MoAb was decreased during HIV-1 infection and was besides CD4(+) T cell numbers the only independent predictor for progression to AIDS. Compared with the group with high CD4(+) T cell numbers the relative risk (RR) for the group with intermediate levels was 2.28, with low levels 5.20. In the groups with intermediate and low CD3 plus CD28 responses the RR was 2.04 and 4.16, respectively. The combined RR for both was 4.65 and 21.63. The independence of this marker was confirmed when the group with low CD4(+) T cell numbers was subdivided into groups with high, intermediate and low T cell responses. The expansion of CD8(+)CD28(-) T cells was already apparent in HIV- homosexual men, but CD8(+)CD28(+) T cells specifically decreased in patients with AIDS. CD28 expression on T cells correlated moderately with T cell responses to CD3 plus CD28 MoAb. T cell reactivity to CD3 MoAb in the presence of CD28 MoAb is a stronger prognostic marker than T cell reactivity to CD3 MoAb alone.