Brucella abortus stimulates human T cells from uninfected and HIV-infected individuals to secrete IFN gamma: implications for use of Brucella abortus as a carrier in development of human vaccines.
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-gamma (IFN gamma). 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 IFN gamma secretion since their removal resulted in increased responses, whereas adding monocytes back to cultures caused inhibition. BA elicited IFN gamma from CD4+ and CD8+ T cells, although CD4+ T cells secrete significantly more (p less than 0.05) IFN gamma than CD8+ T cells. The ability of BA to elicit IFN gamma 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 IFN gamma secretion. Detectable IL-2 secretion was induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically with BA to enhance IFN gamma secretion, suggesting that the amount of IL-2 released by BA alone was insufficient for optimal IFN gamma 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 IFN gamma 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 IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Hematology, U.S. Food and Drug Administration, Bethesda, MD 20892.
R
R
Blay
D
D
Hernandez
M
M
Betts
M
M
Clerici
D R
DR
Lucey
C
C
Hendrix
T
T
Hoffman
B
B
Golding
D002003:Brucella abortus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology*
D016827:CD8 Antigens; D015375:Receptors, Interleukin-2; D014765:Viral Vaccines; D007371:Interferon-gamma