Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection is associated with elevated levels of inflammatory cytokines in the serum and cerebrospinal fluid of infected persons, but the sources of these proteins as well as the specific stimuli which trigger their production and release have not been fully defined. In this study, we evaluated the ability of HIV-1-specific cytotoxic T-lymphocyte (CTL) clones derived from seropositive persons to release gamma interferon (IFN-y), tumor necrosis factor alpha (TNF-a), and TNF-13 upon contact with target cells presenting viral antigen. Peripheral blood-and cerebrospinal fluid-derived HIV-1-specific CD3+ CD4-CD8+ CTL clones as well as freshly isolated peripheral blood mononuclear cells from infected persons were tested in parallel for HIV-1-specific cytotoxicity and cytokine release. Target cells consisted of autologous and allogeneic B-lymphoblastoid cell lines sensitized with synthetic HIV-1 peptides containing the epitopes recognized by these CTL. Cytokine production was measured by specific enzyme-linked immunosorbent assay of culture supernatant fluid. HIV-1-specific CTL clones directed at envelope, Gag, reverse transcriptase, and

Cytokines from Lymphoid Organs of HIV‐infected Patients: Production and Role in the Immune Disequilibrium of the Disease and in the Development of B Lymphomas

“…Double-labeling experiments combining and in situ hybridization showed that the vast majority of IFN-y gene-expressing cells in lymph nodes from HIVinfected patients were not CD4" T-he!per lymphocytes but rather CD8'' T cells (Emilie et al 1990). This observation in lymphoid organs is in agreement with more recent data showing that HIV-specific CDS"" cytotoxic T-lymphocyte (CTL) clones obtained from cerebrospinal fluid from HIV-infected patients produce IFN-7 when challenged with HIV antigen-presenting cells (Jassoy et al 1993). It is also in keeping with the finding that HlV-specific CTL are present in lymphoid organs from HIV-infected patients (Hadida et a!.…”

Intracellular cytokine production by human CD4+ and CD8+ T cells from normal and immunodeficient donors using directly conjugated anti-cytokine antibodies and three-colour flow cytometry

“…In conclusion, we have found no evidence of a defect in IL-2 or TNFin CVID, unlike IFN-. The increase in numbers of cells able to make IFNin CVID would be compatible with a chronic viral infection, as has been described with HIV [27]. However, since no one virus has been implicated in CVID, it is possible that a # 1996 Blackwell Science Ltd, Clinical and Experimental Immunology, 105:517-522 Fig.…”

RANTES Production in HIV‐1 Antigen‐Stimulated Whole Blood Culture: Relationship with Type 1 Immune Response and Plasma Viral Load in Individuals Infected with HIV‐1

“…However, an association between a type 1 immune response to HIV-1 antigens and a restricted virus expression has been suggested by Clerici et al, who recently obtained a dominant type 1 cytokine profile together with a reduced prevalence of HIV-1 isolation in vitro [2]. RANTES and other chemokines, in addition to cytokines like IFN-g, may control HIV-1 directly or indirectly through the attraction and activation of effector cells [4,19,20]. Our study of the relationship between production of RANTES in HIV-1 p24-activated whole blood cultures and the plasma viral load support the hypothesis of the important role of an immune response of gag-specific T cells to restrict virus expression.…”