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IN VITRO EFFECT OF FOSCARNET ON EXPANSION OF T-CELLS FROM PEOPLE WITH LAS AND AIDS

1985; Elsevier BV; Volume: 326; Issue: 8464 Linguagem: Inglês

10.1016/s0140-6736(85)90719-6

1474-547X

JohnC. Beldekas, ElinorM. Levy, Paul H. Black, GeoVon Krogh, Eric Sandström,

HIV Research and Treatment

The drug foscarnet (trisodium phosphonoformate) has been shown to be effective against human T-lymphotropic virus type III (HTLV-III) in a dose-dependent manner when added to infected H-9 cultures. The in vivo effect of foscarnet on T-lymphocyte numbers in acquired immunodeficiency syndrome (AIDS) and lymphadenopathy syndrome (LAS) remains to be evaluated. The authors have found that T cells from individuals with AIDS and LAS display a decreased ability to expand in a T-cell colony assay necessitating clonal expansion for the amplification of antigen specific responder cells and for the general expansion of immature precursor T cells. When foscarnet is added to peripheral blood lymphocytes in soft agar in the presence of PHA and IL-2 there is little change in colony formation in cultured cells from healthy individuals. However in cells from patients with LAS in whom T-cell colony forming ability is diminished foscarnet produces a significant increase in T-cell colony number from 67 + or - 11 to 109 + or - 20. In addition 7 out of 12 AIDS patients showed a positive response to foscarnet despite the fact that their capacity to produce T-cell colonies is diminished even further. AIDS patients given foscarnet showed increases in T-cell colony numbers from 41 + or - 17 to 77 + or - 19. AIDS patients who responded positively to foscarnet showed a significant decrease in T-cell colony numbers when cells were grown in the presence of alpha-interferon. The mechanism by which foscarnet permits T-cell expansion is unclear. It could be allowing infected colony precursors to be activated without going through a cycle of virus production and infection of other T cells or it may inhibit production of suppressive factors that downregulate the immune system. It is concluded that foscarnet might allow populations of peripheral mononuclear cells to expand in vivo thus shifting the equilibrium of AIDS.