AEGiS-11IAC: Low T cell reactivity to combined CD3 plus CD28 stimulation is predictive for progression to AIDS: correlation with decreased CD28 expression.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

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

Int Conf AIDS 1996 Jul 7-12; 11:226 (abstract no. Tu.A.384)
Roos MT, Miedema F, Dekker L, Hooibrink B, de Leeuw NA, Lange JM, Coutinho RA, Schellekens P; Clin. Viro-Immunol., Central Lab. Neth. Red Cross Blood Transf. Serv. and Lab. for Exp. & Clin. Immunol. of the Univ. of Amsterdam, Amsterdam, The Netherlands. Fax: + 31 20 512 3310.

Objective and methods: In 219 HIV+ men of the Amsterdam cohort CD4+ T cell counts, expression of CD28 on CD4+ and CD8+ T cells and T cell responses to CD3 monoclonal antibodies (mAb) with or without CD28 costimulation were analyzed as parameters for disease progression within 4 years. In an additional study in the above mentioned cell populations proliferation and also apoptosis were measured by staining with either Ki-67 or propidium iodide.

RESULTS: CD28 costimulation considerably enhanced responses with lower coefficients of variation. These responses decreased during HIV-1 infection and were a stronger predictive marker for progression to AIDS than responses to CD3 mAb alone. In a Cox analysis, besides CD4+ T cell counts, reactivity to CD3 plus CD28 mAbs was the only independent predictive marker with a relative risk of 2.04 and 4.16 for intermediate and low responses. This independence was confirmed when the group with low CD4+ T cell counts was subdivided into groups with high, intermediate and low T cell responses. It is generally assumed that the CD8+CD28- T cells expand during HIV-1 infection. We provide evidence, that this expansion is only relative and mainly due to a decrease in the number of CD8+CD28+ T cells. CD28 expression on CD4+ and CD8+ T cells correlated with CD28 costimulation. However, CD28 expression failed to reach significance as an independent prognostic marker. Ki-67 expression indicated that the CD8+/CD28- cells proliferated very weakly. The responses of CD8+CD28+ cells were less impaired than those of the CD4+ cells. After stimulation apoptosis was clearly demonstrable in the CD8+CD28+Ki-67- population.

CONCLUSION: Besides CD4+ T cell counts only T cell reactivity to CD3 plus CD28 mAbs was independently predictive for disease progression. The diminished reactivity was mainly confined to the CD4+ T cell population and correlated weakly with CD28 expression on CD4+ and CD8+ T cells.

Keywords: AEGIS, Antigens, CD28, Antigens, CD3, Acquired Immunodeficiency Syndrome, T-Lymphocytes, HIV Infections, CD4 Lymphocyte Count, Antigens, CD8, HIV, Disease Progression, Antigens, CD4, Biological Markers, Anti-HIV Agents, Antibodies, Monoclonal, Human, Male, ICA11

960707
TuA384