Interferon-gamma (IFN-γ) can counteract the in vitro inhibitory effect of an HIV p24 immunosuppressive heptapeptide

Abstract

SUMMARYPrevious work from our laboratory demonstrated that a synthetic heptapeptide (Ch7), corresponding to a conserved sequence of HIV core protein p24 (aa 232-238), was able to specifically abrogate antigeninduced responses in cultures of normal human peripheral blood lymphocytes (PBL). In the present study we show that Ch7 did not inhibit the induction of IFN-°-secreting cells nor the accumulation of IFN-°mRNA in antigen-stimulated cultures. However, delayed addition of recombinant human IFN-°t o Ch7-suppressed cultures was able to restore fully the capacity to mount an antigen-specific antibody response. Thus, although the Ch7 immunosuppressive effect may not be directly related to a decreased production of IFN-°, an increased level of this cytokine is certainly able to counteract the negative effect of the peptide.

Interleukin‐12 up‐regulates the induction of an antigen‐specific antibody response in cultures of human lymphocytes

“…Moreover, IL-12 and IL-12-induced IFN-y act on antigenstimulated T cells to favor differentiation and proliferation of cells with a Thl phenotype [27-291. In our culture system, the induction of a specific anti-SRBC response was previously shown to be IL-2-and IFN-y-dependent [17,25] and to be down-regulated by IL-4 and IL-10 (unpublished results), in line with reported effects of these cytokines . Thus, the up-regulatory effect of IL-12 described in this paper could be a direct consequence of its IFN-yinducing capacity and of its role in the generation of Thl cells.…”

HIV-1 Nef protein inhibits thein vitroinduction of a specific antibody response toCandida albicansby an early up-regulation of IL-15 production

“…Similar immunosuppressive effects have been ascribed to the HIV‐1 Tat protein [6,7]. Moreover, a synthetic heptapeptide corresponding to a conserved sequence of protein p24 was shown to inhibit antigen‐induced responses in cultures of human peripheral blood mononuclear cells (PBMC) and the immunosuppression was mediated by an up‐regulation of prostaglandin E 2 (PGE 2 ) production and cytokine dysregulation [8,9].…”

Possible Role of the Plasminogen Receptor as a Site of Interaction of the Human Immunodeficiency Virus p24 Immunosuppressive Heptapeptide Ch7 with the Host Immune System

“…How Ch7 binding to the plasminogen receptor will finally result in increased PGE 2 production, cytokine dysregulation and suppression of the induction of a specific antibody response, as shown in our laboratory [4][5][6][7], remains to be investigated. Moreover, it has not been established whether interference with the plasminogen activation pathway may also be involved and perhaps play a role in some aspect of the AIDS pathogenesis.…”

“…We showed that a synthetic heptapeptide (Ch7), corresponding to this epitope, specifically abrogated antigen-induced responses in cultures of normal human peripheral blood mononuclear cells (PBMC) as well as PBMC activation induced by anti-CD3, without affecting mitogen-induced proliferation or polyclonal immunoglobulin production [4,5]. Evidence was given that a cytokine imbalance may be at the basis of the Ch7 immunosuppressive activity [6,7]. The immunoregulatory effects of the peptide were shown to be prostaglandin E 2 (PGE 2 )-mediated.…”