These data indicated that RBP2 likely plays a role in cellular migration

oth acute and chronic HIV-1 infection. Furthermore, we found that approximately 100% of patients’ IgM+ rCD4s were also coated with iC3b complement fragments, known as C3 opsonization, suggesting that cellbound IgM is capable of fixing complement and that IgM+ iC3b+ rCD4s may induce stronger ADCP activity by macrophages than IgG+ rCD4s. CD4 MedChemExpress CVT-3146 molecules on CD4+ T cells play an important role in forming the immunological synapse between CD4+ T cells and antigen-presenting cells. However, the attachment of ICs to CD4 molecules could interfere with normal immunological synapse formation between CD4+ T cells and antigen-presenting cells and suppress the full activation of CD4+ T cells. Therefore, our findings here can also be extended to explain the reduced immune function of CD4s in HIV-1+ Pts. However, future studies are needed to confirm this possibility. In Fig. 7, we summarized our hypothesis of the mechanisms of sIC formation on rCD4s and their effects on the dynamics of rCD4 circulation. In our model, the length of time that sICs remain on rCD4s was extremely long compared with CD4s that are circulating between the LNs; as a result, rCD4s continue to be exposed to high concentrations of HIV-1 in the lymphoid organs. Therefore, the percentages and levels of sICs on rCD4s equilibrate to HIV-1 production in the lymphoid organs. However, sIC+ rCD4s are also subject to immunological pressure from both macrophages and NK cells. Therefore, the percentages and levels of sICs on rCD4s were also at equilibrium with the degree of immunological pressure. Collectively, the percentages and levels of sICs on rCD4s in blood appear to reflect a complex interplay between the levels of virus production in lymphoid tissues, the levels of anti-env Abs, the rate of sIC removal from the cell surface, the duration of repeated exposures to HIV-1/gp120 or ICs, and the degree of immunological elimination and trapping of sIC+ rCD4s from peripheral circulation. Because ART may not dramatically influence sIC turnover rates on rCD4s, the levels of anti-env Abs, and the duration of CD4+ T cell circulation among lymphoid tissues, changes in the percentage of sIC+ rCD4s in the blood after initiation of ART may reflect the level of virus production in lymphoid tissues and the degree of immune pressure on sIC+ rCD4s. Importantly, our hypothesis here is highly consistent with the previously proposed mathematical model that suggests that the effects of HIV-1 on resting T lymphocytes can explain the depletion of CD4+ T cells from the peripheral blood during HIV-1 infection. When we analyzed the percentages of sIC+ rCD4s in blood, sIC+ rCD4s were detectable in peripheral blood after approximately 2 yrs of complete suppression of plasma VL. Effective ART has been shown to rapidly reduce the levels of both plasma VL and HIV-1-producing cells to undetectable levels; however, HIV-1 replication continues in LNs in patients with undetectable plasma VLs after PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19649022 ART. If we assume that ART treatment does not significantly change the degree of immunological pressure on sIC+ rCD4s in our model, the number of sIC+ rCD4s should mainly reflect residual viral production in LNs. Therefore, monitoring the percentage of sIC+ rCD4s in peripheral blood may be a promising tool to examine residual virus replication in patients with undetectable plasma virus levels under ART. More importantly, sIC+ rCD4s in blood were only found in HIV-1+ Pts; we did not find sIC+ rCD4s in healthy donors or any patien