MEASUREMENT OF CD69 INDUCTION IN THE ASSESSMENT OF IMMUNE FUNCTION INASYMPTOMATIC HIV-INFECTED INDIVIDUALS

Peripheral blood mononuclear cells from many asymptomatic HIV-infected patients exhibit defects in cytokine production and impaired prolifer ative responses in vitro hut the mechanisms underlying this subclinica l immune deficiency are controversial, To determine whether abnormalit ies in the earliest events following receptor engagement may help to e xplain the in vitro immune dysfunction, we measured the inducibility o f the early activation marker CD69 in T cells from asymptomatic HIV-in fected individuals in response to stimulation with anti-CD2 or anti-CD 3 mAb, In a whole blood assay, we found that induction of CD69 was mar kedly impaired in CD4(+) T cells from later-stage HIV-infected patient s (CD4 counts 200-400/mm(3)) compared to uninfected controls, Among ea rly stage patients (CD4 > 400/mm(3)), a subset (29%) had impaired CD69 induction, CD69 responses were equally depressed after stimulation th rough the CD3 or CD2 receptor pathways, Survey of a panel of immunophe notypic markers and propensity for apoptosis demonstrated a significan t association between depressed induction of CD69 and decreased percen tages of CD4(+)CD26(+) and CD4(+) CD95(+) cells but no association wit h the level of apoptosis. These data indicate that defects in T lympho cyte activation through CD3 and CD2 can he measured within hours of re ceptor stimulation in asymptomatic HIV-infected individuals and might be useful to monitor as an indicator of immune function in these patie nts. (C) 1997 Wiley-Liss, Inc.