Since we are considering Brucella abortus (BA) as a carrier for human vaccines, especially for HIV-1 infected persons, it was important to know what effect it had on human T cells. Evidence from murine studies, performed in vivo, suggested that repeated BA injections caused interferon- gamma (IFNy) release and expansion of TH1 cells. We found that human T cells (85-95% CD3+ by flow cytometry) secred IFNy in response to BA and lipopolysaccharide (LPS) from BA. This response to BA was increased synergistically in the presence of IL-2. Both CD4+ and CD8+ T cells, separated by panning, released IFNy when stimulated by BA. T cells from HIV-1 infected asympotmatic persons were also able to respond to BA and secrete IFNy. However, T cells from patients with symptoms were only responsive if IL-2 was present. IFNy has been shown to be a product of TH1 cells, IL-4 secretion, which is a function of TH2 cells, was assessed using a cell line (CtH4), cells stimulated by BA did not induce proliferation of CtH4, which was sensitive to the presence of 10 pg/ml of IL-4. Similarily, no IL-4 was detected in these supernatants in the ELISA, which was sensitive to 30 pg/ml of IL-4. These results were confirmed by PCR analysis, which showed that BA induced IFNy, but not IL-4 mRNA. These data suggest that BA LPS from BA are capable of selectively stimulating human TH1 cells. This has important implications in vaccine development since a TH1 cell bias may afford greater protection against certain infections including HIV-1.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BH002009-03
Application #
3792633
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Center Biologics Evaluation Research Hematology
Department
Type
DUNS #
City
State
Country
United States
Zip Code