Combined use of an immunotoxin and cyclosporine to prevent both activated and quiescent peripheral blood T cells from producing type 1 human immunodeficiency virus.

Abstract

Two different populations of infected T cells are present in human immunodeficiency virus (HIV)-infected individuals: activated cells that produce virions and quiescent cells that harbor the viral genome but are unable to produce virus unless they are activated. Using an in vitro model of acute HIV infection, we have evaluated the effect of depleting activated T cells with an immunotoxin and subsequently inhibiting activation of quiescent T cells with an immunosuppressive agent. CD25 (Tac, p55), the alpha chain of the interleukin 2 receptor, is expressed on activated, but not quiescent, T cells. An anti-CD25-ricin A chain immunotoxin eliminated activated, CD25+ HIV-infected cells and, thereby, inhibited viral production by these cells. Subsequent addition of cyclosporine to the residual CD25- cells prevented their activation and thereby suppressed their ability to produce virus and to propagate the infection to uninfected T cells.

In Vivo Efficacy of Anti-Glycoprotein 41, But Not Anti-Glycoprotein 120, Immunotoxins in a Mouse Model of HIV Infection

“…ITs have been proposed as a treatment for HIV infection. They may be targeted either to cell types known to be sites of HIV replication (1)(2)(3) or to actively infected cells expressing the HIV envelope protein(s) gp160, gp120, and gp41 on the cell surface. These anti-HIV ITs may be targeted with either CD4 (4 -6) or with mAbs (7)(8)(9)(10).…”

Zidovudine, Lamivudine, and Abacavir Have Different Effects on Resting Cells Infected with Human Immunodeficiency Virus In Vitro

“…By doing so, drug concentrations should not be a limiting factor when evaluating their activities in resting cells. This in vitro model was previously used to characterize the anti-HIV activity of cyclosporine and other immunomodulatory agents that had a clear effect on latently infected cells (1,3). Others have used p24 production to evaluate different NRTIs in unfractionated in vitro HIV-infected PBMCs (36), but this is the first study to examine the activity of nucleoside analogs based on virus production.…”

“…To assess the effect of treatment with IT alone, we included two groups of cells without NRTIs but incubated with either CM or CM plus IT. p24 production was determined after PHA activation, since CD25 Ϫ cells do not produce virus unless they are activated (1,5,31). Nevertheless, we compared each culture of resting CD25…”

“…Initial dilutions were based on the 50% inhibitory concentrations for viral isolates, and based on preliminary experiments, we used 0.01 to 0.15 M ZDV, 0.25 to 5 M 3TC, and 2 to 15 M ABC. The anti-CD25 IT, RFT5-dgA, was prepared and purified as previously described (1,3,27).…”

Site-directed serology of HIV-1 subtype B infection: relation between virus specific antibody levels and disease progression

“…The seemingly general impairment is likely to be caused by the early infection and killing, and subsequent dysfunction, of activated HIV-1-specific Th cells as well as other Th cell populations activated at the same time. We know from in vitro studies that HIV-1 replicates more efficiently in activated Th cells [14]. Activated Th cells multiply by clonal expansion.…”