Cytokines from vaccine-induced HIV-1 specific cytotoxic T lymphocytes: Effects on viral replication

Robert C Bollinger, Thomas C Quinn, A. Y. Liu, P. E. Stanhope, S. A. Hammond, R. Viveen, M. L. Clements, Robert F Siliciano

Research output: Contribution to journalArticle

Abstract

Cytolytic T lymphocytes (CTLs) specific for the human immunodeficiency virus (HIV-1) envelope glycoproteins have been cloned from HIV-1-seronegative human volunteers immunized with HIV-1 gp160-based candidate vaccines. Although vaccine-induced CTLs can potentially contribute to the antiviral response by direct lysis of infected cells, these CTLs may also produce cytokines that alter HIV-1 gene expression in other infected cells present in the microenvironment where CTL-target cell interactions occur. Vaccine- induced CTL clones were therefore examined for production of cytokines that affect HIV-1 gene expression in chronically infected T lymphocytic and promonocytic cell lines. Enhancement of HIV-1 gene expression was observed with supernatants from CD4+ CTL clones and with supernatants from a subset of CD8+ CTL clones. For each clone studied, upregulation of HIV-1 gene expression in chronically infected T cell lines resulted from the antigen- specific release by CTLs of tumor necrosis factor α (TNF-α). CD4+ and CD8+ CTLs that released TNF-α on antigen stimulation were also shown to express a biologically active 26-kDa transmembrane form of TNF-α, which was sufficient to induce upregulation of HIV-1 gene expression in chronically infected T cells placed in direct contact with the CTLs. Supernatants from antigen-activated, vaccine-induced CD4+ and CD8+ CTLs also caused upregulation of HIV-1 gene expression in chronically infected promonocytic cells. A subset of CD8+ CTL clones also produced a soluble factor(s) that inhibited HIV-1 replication in acutely infected autologous CD4+ blasts. Supernatants from CD4+ CTLs had no effect on HIV-1 replication in acutely infected CD4+ blasts. These results suggest that cytokine production as well as cytolytic activity should be evaluated in the analysis of the potential antiviral effects of vaccine-induced CTLs.

Original languageEnglish (US)
Pages (from-to)1067-1077
Number of pages11
JournalAIDS Research and Human Retroviruses
Volume9
Issue number11
StatePublished - 1993

Fingerprint

Cytotoxic T-Lymphocytes
HIV-1
Vaccines
Cytokines
T-Lymphocytes
Gene Expression
Clone Cells
Up-Regulation
Tumor Necrosis Factor-alpha
Antigens
Antiviral Agents
Cell Line
Cell Communication

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Cytokines from vaccine-induced HIV-1 specific cytotoxic T lymphocytes : Effects on viral replication. / Bollinger, Robert C; Quinn, Thomas C; Liu, A. Y.; Stanhope, P. E.; Hammond, S. A.; Viveen, R.; Clements, M. L.; Siliciano, Robert F.

In: AIDS Research and Human Retroviruses, Vol. 9, No. 11, 1993, p. 1067-1077.

Research output: Contribution to journalArticle

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