. The investigator has develped a model of immune deficiency that demonstrates the essential role of IFN gamma in the immune response to mycobacterial infection. Since IFN gamma plays a critical role in host defense against mycobacterial infection, the investigator would like to elucidate the mechanisms of action of IFN gamma in cell-mediated immunity. She will compare the immune response to BCG in normal and IFN gamma knockout mice. Any difference in the immune response of these two groups of mice will be the result of the presence or absence of IFN gamma. She will determine which cytokine profiles are produced during the protective immune response to mycobacterial infection. Since the investigator has observed poor granuloma formation and decreased expression of the chemokines RANTES and MIF in the IFN gamma knockout mice, she will investigate whether IFN gamma regulates granuloma formation through the induction of chemokine gene expression. The chemokines may then attract monocytes to the site of granuloma formation. A number of suppressive activities of IFN gamma have been observed in vitro. The investigator's analysis of the immune response of IFN gamma knockout mice to mycobacteria suggest that IFN gamma may have suppressive activity during an in vivo immune response. She will test, in IFN gamma knockout mice, whether B cells, T cells and hematopoietic progenitor cells undergo extensive proliferation in vivo during infection with mycobacteria. IFN gamma exerts its regulatory effects on the immune response by signalling to target cells to express genes. She will use the technique of differential display of mRNA, comparing BCG-infected livers in IFN gamma knockout and control mice, to identify genes that are regulated by IFN gamma during the immune response to mycobacteria. The investigator believes that these studies will provide insight into the mechanisms of protective immune response to mycobacterial infection and may highlight potential therapeutic strategies to augment immunity to these pathogens.
| Dalton, D K; Haynes, L; Chu, C Q et al. (2000) Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells. J Exp Med 192:117-22 |
| Chu, C Q; Wittmer, S; Dalton, D K (2000) Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J Exp Med 192:123-8 |
