Slow turnover of HIV-1 receptors on quiescent CD4+ T cells causes prolonged surface retention of gp120 immune complexes in vivo.

Peripheral blood CD4(+) T cells in HIV-1(+) patients are coated with Ig. However, the causes and consequences of the presence of Ig(+) CD4(+) T cells remain unknown. Previous studies have demonstrated the rapid turnover of viral receptors (VRs) on lymphoma and tumor cells. The present study investigates the turnover of VRs on peripheral quiescent CD4(+) T cells (qCD4s), which are the most abundant peripheral blood CD4(+) T cells. Utilizing pharmacological and immunological approaches, we found that the turnover of VRs on qCD4s is extremely slow. As a result, exposure to gp120 or HIV-1 virions in vitro causes gp120 to remain on the surface for a long period of time. It requires approximately three days for cell-bound gp120 on the surface to be reduced by 50%. In the presence of patient serum, gp120 forms surface immune complexes (ICs) that are also retained for a long time. Indeed, when examining the percentages of Ig(+) CD4(+) T cells at different stages of HIV-1 infection, approximately 70% of peripheral resting CD4(+) T cells (rCD4s) were coated with surface VRs bound to slow-turnover gp120-Ig. The levels of circulating ICs in patient serum were insufficient to form surface ICs on qCD4s, suggesting that surface ICs on qCD4s require much higher concentrations of HIV-1 exposure such as might be found in lymph nodes. In the presence of macrophages, Ig(+) CD4(+) T cells generated in vitro or directly isolated from HIV-1(+) patients were ultimately phagocytosed. Similarly, the frequencies and percentages of Ig(+) rCD4s were significantly increased in an HIV-1(+) patient after splenectomy, indicating that Ig(+) rCD4s might be removed from circulation and that non-neutralizing anti-envelope antibodies could play a detrimental role in HIV-1 pathogenesis. These findings provide novel insights for vaccine development and a rationale for using Ig(+) rCD4 levels as an independent clinical marker.