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Downregulation of interferon alpha but not gamma receptor expression in vivo in the acquired immunodeficiency syndrome


, : Downregulation of interferon alpha but not gamma receptor expression in vivo in the acquired immunodeficiency syndrome. Journal of Clinical Investigation 82(4): 1415-1421

Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. In evaluating the role of IFN as therapeutic agents in AIDS, we investigated the expression of IFN.alpha. and .gamma. receptors on peripheral blood mononuclear cells (PBM) from patients with AIDS, ARC, and heterosexual control subjects using radioiodinated IFN.alpha.2 and IFN.gamma. The binding characteristics of the 125I-IFN.alpha. and .gamma. to PBM were analyzed to determine receptor numbers and dissociation constants. PBM from controls expressed 498 .+-. 247 IFN.alpha. receptor sites/cell (n = 17). However, eight patients with ARC and seven patients with AIDS had a mean number of IFN.alpha. receptor/cell of 286 .+-. 235 (P < 0.05) and 92 .+-. 88 (P < 0.001), respectively. This was consistent with elevated levels of serum acid-labile IFN.alpha. and cellular 2-5A synthetase activity in patients. Treatment of PBM from the AIDS patients with exogenous IFN.alpha. in vitro resulted in minimal 2-5A synthetase induction in comparison to controls. In contrast, the expression of IFN.gamma. receptors in ARC (n = 5) and AIDS (n = 4) patients remained normal. Thus the decrease in IFN.alpha. receptor expression and consequent hyporesponsiveness to IFN.alpha. raises the question of the usefulness of INF.alpha. therapy in end-stage AIDS. The normal expression of IFN.gamma.-receptors in AIDS patients suggests that IFN.gamma. may prove useful in attempts to provide immune reconstitution.

US$19.90

PMID: 2971677

DOI: 10.1172/JCI113746


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