The expression of different T helper (TH) lymphocyte phenotypes is primed upon antigen presentation and is reciprocally mediated by the initiation cytokines IL-12 for TH1 expression and IL-4 for TH2 expression. TH phenotype expression has recently been associated with the outcome of human immunodeficiency virus (HIV) infection. Some individuals belonging to high risk groups repeatedly exposed to HIV remain antigen and antibody negative while exhibiting strong TH1 responses to a HIV env peptide representing a T-cell epitope. Furthermore, the development of immunodeficiency correlates with the progressive loss of TH1 phenotype expression, while TH2 phenotype expression becomes more dominant. However, the role of the TH1 phenotype in immune protection to natural retroviral disease in humans and other outbred species has not been directly tested experimentally. It is proposed to initiate the TH1 or TH2 phenotype in response to a defined antigen [Bovine Leukemia Virus (BLV) env gp51] in outbred cattle in vivo by coexpression with recombinant bovine (rb) IL-12 or rbIL-4 in a vaccinia vector. This strategy will allow testing of the role of defined TH phenotypes in immune protection to BLV, an exogenous, lymphotropic leukemia virus closely related to HTLV-I and II. The hypothesis that inoculation of cattle with a vaccinia vector coexpressing rbIL-12 and the BLVenv gene will enhance TH1 expression, whereas inoculation with a vaccinia vector coexpressing rbIL-4 and the BLVenv gene will enhance TH2 expression will be tested by 3 specific aims: 1] Express functional recombinant bovine IL-12. 2] Construct vaccinia recombinants expressing the BLVenv gene in combination with rbIL-2 or rbIL-4. 3] Document the cytokine profile expressed by BLV env specific CD4+ lymphocytes primed in cattle inoculated with the recombinant vaccinia vectors defined in aim #2.
| Von Beust, B R; Brown, W C; Estes, D M et al. (1999) Development and in vitro characterization of recombinant vaccinia viruses expressing bovine leukemia virus gp51 in combination with bovine IL4 or IL12. Vaccine 17:384-95 |
