ormed on the cells. Additionally, we excluded the possibility that HIV-1+ Pt serum contains auto-Abs. Importantly, once Ig is lost from the surface of HIV-1+ Pt rCD4s after sustainable cell culture, no sICs formed on 
the surface even when exposed to patient serum, suggesting that rCD4s from HIV-1+ Pts do not express molecules that bind to cICs or selfantigens that react with certain Abs in Pt serum. Collectively, we have excluded the possibility that sICs are formed due to HIV-1+ Pt serum containing sufficient levels of auto-Abs or cICs. Next, to clarify whether gp120 binds to CD4 molecules on rCD4s in vivo in HIV-1+ Pts, we showed that the gp120-binding Frequencies and Numbers of sIC+ Resting CD4+ T Cells in Blood Increase after Spleen Removal Finally, we performed a longitudinal analysis of sIC+ rCD4 levels in peripheral blood from an HIV-1-infected hemophiliac Dynamics of Immune Complexes on Resting T Cells domain of CD4 was occupied in rCD4s from HIV-1+ Pts, thereby indirectly demonstrating that gp120 is attached to CD4 on rCD4s in vivo. Furthermore, we showed that anti-env Abs directly bound to rCD4s from an HIV-1-infected individual whose anti-gp120 Ab levels were below the sensitivity of a conventional western blotting test. Collectively, we conclude that sICs on rCD4s in HIV-1+ Pts result from CD4-bound gp120. However, we can hypothesize that cell-bound gp120 could reflect the production of HIV-1 in rCD4s. In this respect, it is well established that direct infection of rCD4s does not lead to productive infection, instead, resulting in a labile state known as preintegration latency. Therefore, gp120 attached to CD4 is not linked to HIV-1 production by rCD4s. In contrast, in vitro culture of purified rCD4s from HIV-1+ Pts revealed that a 50% reduction in sICs on rCD4s required approximately 20 h due to the slow turnover of VRs on rCD4s. Therefore, the half-life of sICs on rCD4s is much longer than the duration on CD4+ T cells recirculating between LNs and the peripheral blood. Before sICs disappear from the surface, rCD4s may be continuously exposed to gp120 and/or HIV-1 at high concentrations in the lymphoid organs. Thus, the levels and percentages of sIC+ rCD4s may become equilibrated to the levels of virus production and/or anti-HIV-1 Abs in the lymphoid organs. To clarify the pathological effects of sICs on rCD4s, we demonstrated here that sIC+ rCD4s produced in vitro or isolated from HIV-1+ Pts ultimately induced ADCP and ADCC by autologous macrophages and NK cells, respectively. Furthermore, the phagocytic activities of monocytes as measured directly using Fc-OxyBurst assays on BHI-1 web freshly isolated monocytes from HIV-1+ Pts were even stronger in the healthy donors. Therefore, these results suggest that sIC+ rCD4s in peripheral blood may be destroyed and removed from circulation at a constant rate. Dynamics of Immune Complexes on Resting T Cells 11 Dynamics of Immune Complexes on Resting T Cells We found PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19649022 that the percentages of sIC+ rCD4s in HIV-1+ Pts were inversely correlated with the number of CD4+ T cells in the blood. Furthermore, we found that in an HIV-1-infected individual whose VL became undetectable with ART, the percentage and number of sIC+ rCD4s in blood gradually decreased but promptly increased after splenectomy. Therefore, we can hypothesize that sIC+ rCD4s may be destroyed and removed from circulation by macrophages or NK cells in the spleen or other lymphoid organs. Indeed, splenomegaly is a common symptom of b