Brucella abortus Stimulates Human T Cells from Uninfected and HIV-infected Individuals to Secrete IFNγ: Implications for Use of Brucella abortus as a Carrier in Development of Human Vaccines

Roy Blay, Diana Hernandez, Michael Betts, Mario Clerici, Daniel R. Lucey, Craig Hendrix, Thomas Hoffman, Basil Golding

Research output: Contribution to journalArticlepeer-review

Abstract

Brucella abortus has been characterized as a T-independent type 1 antigen/carrier in human and murine antibody responses. In this report it is shown that BA can activate human CD3+ T cells to secrete interferon-γ (IFNγ). Unlike mitogens, such as phytohemagglutinin, this stimulation was associated with minimal T-cell proliferation or upregulation of interleukin-2 (IL-2) receptor. Monocytes inhibited BA-mediated IFNγ secretion since their removal resulted in increased responses, whereas adding monocytes back to cultures caused inhibition. BA elicited IFNγ from CD4+ and CD8+ T cells, although CD4+ T cells secrete significantly more (p<0.05) IFNγ than CD8+ T cells. The ability of BA to elicit IFNγ from human T cells was inhibited in the presence of anti-Tac, suggesting that BA also induces IL-2 secretion and that IL-2 is involved in BA-mediated IFNγ secretion. Detectable IL-2 secretion was induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically with BA to enhance IFNγ secretion, suggesting that the amount of IL-2 released by BA alone was insufficient for optimal IFNγ release. Furthermore, addition of IL-2 to T cells from individuals with poor or absent responses to BA, including individuals infected with HIV-1, restored their ability to secrete IFNγ in response to BA. These data indicate that BA is capable not only of activating human B cells but can also induce T cells, probably of the TH1 phenotype, to secrete IFNγ. Production of IFNγ in response to BA has implications in the proposed development of BA as a carrier for human vaccines, since IFNγhas multiple effects including macrophage activation, B-cell differentiation, and antiviral activity.

Original languageEnglish (US)
Pages (from-to)479-486
Number of pages8
JournalAIDS research and human retroviruses
Volume8
Issue number4
DOIs
StatePublished - Apr 1992
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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