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

Abstract

SUMMARYIn 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 ( 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 ÿ T cells was already apparent in HIV ÿ 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.

Restoration of Normal Interleukin‐2 Production by CD4+T Cells of Human Immunodeficiency Virus–Infected Patients after 9 Months of Highly Active Antiretroviral Therapy

“…CD8 lymphocytosis, which is commonly seen in HIV-seropositive individuals, consists of CD28 Ϫ cells expressing activation markers such as HLA-DR, CD38, and CD45RO [29,30]. We observed a decrease in CD8 ϩ CD28 Ϫ T cells during HAART.…”

Nonradioactive Techniques for Measurement of In Vitro T-Cell Proliferation: Alternatives to the [3H]Thymidine Incorporation Assay

“…It has been reported that T-cell proliferation in response to stimulation with CD3 and CD3ϩCD28 MAbs decreases shortly after seroconversion, before the decline in CD4 ϩ T-cell number is observed (10,23,33). It has also been demonstrated that loss of T-cell reactivity to CD3 and CD3ϩCD28 MAbs in vitro is a strong predictive marker for progression to AIDS, independent of decline in CD4 counts (32,33). Thus, T-cell proliferative capacity is an important independent predictor of progression to HIV disease (31,33) and also can serve to monitor immunological improvement after therapy (1,26).…”

A Low Level of CD4+CD28+T Cells Is an Independent Predictor of High Mortality in Human Immunodeficiency Virus Type 1–Infected Patients

“…It has been demonstrated that low levels of CD4 + CD28 + cells and a low T cell reactivity to CD3/CD28 costimulation predict AIDS [3,18]. Furthermore, the CD4 + CD28 + cell level correlates negatively with various HIV disease progression markers [4].…”