STUDIES OF HUMAN T-HELPER CELL TYPE 1 AND TYPE 2 CYTOKINE RESPONSES

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T helper cells have been divided into different subsets based on the cytokines they secrete. TH0 cells secrete IL2, IL4 and IFN-; TH1 cells secrete IL2 and IFN-; 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. Small resting human T cells were shown to express IFN- and IL2, but not IL4 in terms of protein and mRNA. 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. Since TH1 responses are favored in the presence of IL-12, a monocyte product, we studied whether B. abortus could induce IL- 12 release from human monocytes. PCR of mRNA revealed that B. abortus does elicit IL-12 from monocytes, providing a second pathway for B. abortus to induce a TH1-like response. Cytokines may play a role in the adverse effects seen following treatment with IGIV. This was studied using human T cells and monocytes. IGIV was shown to induce TNFa, IL-1a and IL-6 from human monocytes. These results may explain the fever, headache and low back pain frequently experienced by patients receiving this product.