PubMed · 7355495
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S E Svehag. 1980-01-14. [Circulating immune complexes].. https://pubmed.ncbi.nlm.nih.gov/7355495/
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HIV-1-infected quiescent CD4+ cells harbor the virus in an inactive state until subsequent activation. The possibility that HIV-1 itself and the virus envelope glycoprotein 120 (gp120) might be important agents of this activation was investigated. The present data indicate that binding of heat-inactivated HIV-1 (iHIV-1) to infected resting PBMCs was sufficient to activate NF-kappa B and AP-1, to induce transition from the G0/G1 stage of the cell cycle to the S/G2/M stage, to induce cell surface expression of CD25, to stimulate provirus integration, and to commit cells to produce virus. The cumulative amount of HIV-1 produced by iHIV-1-stimulated cells strictly depended on the concentration of p24gag in the virion preparations used for stimulation. Moreover, virus production was not evidenced in infected resting cells exposed to iHIV-1 previously incubated with soluble CD4 (sCD4), indicating that activation requires a contact between HIV-1 envelope glycoproteins and cell surface CD4. Although soluble gp120 did not stimulate virus production, we found that transition to the S/G2/M stage of the cell cycle, cell surface expression of activation Ags, and virus production were stimulated by cross-linking of CD4 by gp120-anti-gp120 immune complexes. Finally, incubation of gp120-anti-gp120 immune complexes with sCD4 inhibited these effects. These findings suggest that virions and gp120 anti-gp120 immune complexes found in infected patients at all times of infection can stimulate virus production in CD4+ cells harboring HIV-1 in an inducible state.
The ability of Fc gamma R on monocytes and macrophages to enhance presentation of Ab-bound Ag has been well established. In contrast, studies suggest that Fc gamma RII on B cells functions primarily to suppress B cell responses. We found that presentation of tetanus toxoid (TT) by human EBV-transformed B cells was enhanced by 100- to 1000-fold, when TT was targeted to Fc gamma RII on B cells by using a conjugate consisting of TT covalently linked to anti-human Fc gamma RII mAb 41H16. This enhanced presentation could be blocked by mAb 41H16, heat-aggregated human IgG, or anti-MHC Class II mAb. Similarly, multimeric immune complexes composed to TT and anti-TT mAb, SA13, and 9F12 also enhanced presentation of TT. Furthermore, Fc gamma RII on purified human peripheral blood B cells could also enhance Ag presentation. These studies provide the first clear evidence that Fc gamma RII can participate in enhanced Ag presentation by human B cells and suggest that Fc gamma RII has the potential to play a stimulatory role in human B cell responses to Ag-Ab complexes.
We have used two experimental models of immune complexes to study the secretion of interleukin (IL)-10, IL-6 and their connection with the immune complex-induced synthesis of prostaglandin (PG) E2 by human monocytes in vitro. Immune complexes formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum immunoglobulins induced the release of IL-6 and IL-10 in a dose- and antigen: antibody ratio-dependent manner. Antigen-antibody complexes formed near equivalence were most effective in induction of a cytokine response. PGE2 could augment the immune complex-induced IL-6 and IL-10 secretion, but alone, did not induce cytokine secretion. IL-10 was capable of down-regulating the release of IL-6 and PGE2. Additionally, we demonstrated that endogenously synthesized IL-10 limited the immune complex-induced secretion of proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta. All three regulatory factors examined here share anti-inflammatory properties and are closely associated with the T helper type 2 (Th2) immune response. We conclude that immune complexes, besides their well-known ability no cause acute and chronic inflammation, can mediate immunosuppressive effects and influence the balance of Th1/Th2 responses.