T helper cells have been divided into different subsets based on the cytokines they secrete. THO cells secrete IL2, IL4 and IFNgamma; TH1 cells secrete IL2 and IFNgamma; and TH2 cells secrete IL4. Susceptibility to certain infectious diseases has been shown to be dependent on the predominant type of TH cell induced. There is some evidence that progression of HIV-1 infection is associated with a bias towards TH2 cells. Thus, vaccines for HIV-1 infection may be advantageous if they induce anti- HIV immunity by recruiting TH1 rather than TH2 cells. B. abortus has been shown to induce TH1 cells in mice. Since B. abortus can also stimulate human B cells in a T-independent manner we have been studying it as a possible carrier for HIV-1 proteins and peptides as a vaccine. It was therefore of interest to determine what effect B. abortus would have on human T cells. Human T cells were purified by passage of peripheral blood mononuclear cells over nylon wool followed by percoll gradient centrifugation. Small resting T cells were stimulated in the presence of B. abortus and shown to secrete IFNgamma and IL2, but not IL4. Similarly, PCR amplification of RNA from these cells showed that B. abortus induced IFNgamma, IL2 and IL2R mRNA but no IL4 mRNA. The source of the IFNgamma was not from contaminating NK cells because magnetic bead removal of NK cells had no effect on the outcome, and enriched NK cells depleted of T cells did not respond to B. abortus. These results indicate that B. abortus can stimulate TH1 responses from human T cells, and as such may be beneficial as a carrier for persons infected with HIV-1.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BQ004002-01
Application #
3770447
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost