Lectin production by human T-lymphocytes

Cultured human peripheral blood monocytes (PBMC) and the cell line H9 release a lectin. This lectin is not the previously described sarcolectin, since it does not specifically recognize the sugars lactose and sialic acid. The lectinic T-cell factor reduces the release by APCs of IFNα - a key cytokine known to inhibit the proliferation of activated T-lymphocytes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of AIDS pathogenesis? - A model for HIV1-induced immunopathogenesis

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Repair of the in vitro HIV-1-induced immunosuppression and blockade of the generation of functional suppressive CD8 cells by anti-alpha interferon and anti-Tat antibodies

The acute human immunodeficiency virus type 1 (HIV-1) infection of activated peripheral blood mononuclear cells (PBMCs) from normal donors results in inhibition of cell proliferation and generation of functional suppressive T cells. Cultured HIV-1 infected PBMCs but not uninfected PBMCs, following irradiation, can inhibit the proliferation of antigen-activated autologous T cells in a dose-dependent way. CD8' cell subpopulation is responsible for this inhibition. The presence of anti-alpha interferon (IFNα) and anti-Tat antibodies in the culture medium counteracts the HIV-1-induced immunosuppression and prevents the generation of suppressive T cells by these PBMCs. The reported data should have major implications for strategies of AIDS treatment which, in association with antiviral drugs, aim at targetting immune disorders.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Induction of cellular immunosuppression by the human papillomavirus type 16 E7 oncogenic protein

The human papillomavirus type 16 (HPV-16) E7 oncogenic protein is found in the culture supernatant of SiHa cells, a cervical carcinoma cell line. Extracellular E7 protein, acting as a viral toxin in human immune cells, induces the overproduction of the immune suppressive IFN-α cytokine by APCs, and inhibits the T-cell response to recall and allogenic antigens. These effects should be taken into account for the design of anti-human cervical carcinoma vaccines.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pathogenic disorders involved in immunosuppression and T cell depletion characterizing AIDS

Four cardinal immune disorders interacting with each other may promote the progressive T cell depletion and immunosuppression characterizing AIDS. Immune activation of HIV-1 infected T4 cells leads to virus release and premature cell death. Both virus release with its resulting viral load and dead cells are the source of gp120 stimulus. Anergy of non-infected CD4 cells, resulting in cytokine dysregulation may be promoted by impairing the CD4-MHC interaction during CD4 cell activation either directly through the SLWDQ pentapeptide identity with the CD4 molecule and the CD4 binding region or through a gp120-induced autoimmune reaction to CD4. Overproduction of IFNα, the known antiproliferative and cytolytic cytokine may promote in a paracrine manner to neighbouring cells the immunosuppression generated by the lack of IL2 secretion following CD4 cell anergy. Apoptosis of activated non infected T cells could be induced by effector components of the sutoimmune reaction (CTL, Lymphotoxins or Abs?) directed towards the 2 consensus gp120 sequence identity/similarity (INCTR and FYCNST) shared with the APO/Fas molecule. These two sequences are known as immunodominant sites of the gp120. Furthermore, IFNa overproduction may also render circulating memory T cells competent to apoptosis by upregulating the cascade of metabolic events leading to programmed cell death. © 1994.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tat toxoid as a component of a preventive vaccine in seronegative subjects

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

HPV-16 E7 but not E6 oncogenic protein triggers both cellular immunosuppression and angiogenic processes

HPV-16 E6 and E7 oncoproteins impair the cell cycle in human uterine cervix carcinoma cells (HUCC) by acting on p53 and retinoblastoma proteins, respectively. We recently reported that E7 released into the extracellular compartment by HUCC SiHa cells could inhibit immune T-cell response to recall and alloantigens by a mechanism involving an overproduction of the immunosuppressive IFNα by antigen presenting cells (APCs). In this study, we found that besides E7, E6 protein and the vascular endothelium growth factor (VEGF) were released into the SiHa cell supernatants, and we further showed that extracellular E7 but not E6 oncoprotein 1) inhibits the immune cell response to recall and alloantigens, and 2) enhances the release of angiogenic cytokines, including TNFα, IL-1β and IL-6 by macrophages and/or dendritic cells. VEGF unexpectedly released by cancer cells could also contribute to angiogenesis. Thus in HUCC the same E7 oncoprotein which contributes to controlling the cancer cell cycle has the means in its extracellular configuration to contribute to microenvironmental immunosuppressive and angiogenic processes. Neutralizing anti-E7 antibodies either passively administered or induced by active immunization could represent a new immunotherapeutic endeavour to combat the immunosuppression and/or neoangiogenesis effects of extracellular E7 protein.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected patients

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Removal of GP160 induced bio-hazards for a safe AIDS vaccine candidate

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system - anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1 - particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp0000 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs. anti-AIDS vaccine / HIV-1 Env gp160 protein enhancing antibodies / anti-CD4 autoantibodies. © 1992.SCOPUS: ar.jinfo:eu-repo/semantics/publishe