| The purpose of the present studies was to decipher the cellular immune mechanism(s) of protection induced by the dual-subtype FIV vaccine. A total of 22 cats were divided into three groups in the first study: cats immunized with the dual-subtype FIV vaccine; cats immunized with uninfected cell lysate; or cats receiving no vaccination. Cell-mediated immune responses were assessed by measuring FIV-specific mRNA and biological activity levels of Th1/Th2 cytokines and cytotoxins. The types of immune cells that were involved in vaccine protection were also determined by using a magnetic cell separation method with cell phenotype-specific antibodies. Adoptive transfer was performed in the second study with a total of 22 pairs consisting of either MHC-matched or unrelated pairs. This study was further divided into 3 studies that differed by the approach taken to produce MHC-matched pairs and the cell types of the adoptively transferred population.; Overall, both Th1 (IFNgamma, TNFalpha, and IL-2) and Th2 (IL-4 and IL-6) cytokines were detected in all vaccinated cats. No overt polarization towards Th1 or Th2 profiles was found in most cats. Additionally, cells from vaccinated cats proliferated and produced significant levels of mRNA for IFNgamma, IL-2 and perforin upon in vitro stimulation with FIV antigen. Those changes were induced in the T-cell population. Finally, adoptive-transfer recipients of either whole blood or B-cell depleted populations from MHC related/vaccinated cats were protected from homologous FIV strain challenge, whereas recipients of either B-cell enriched population from MHC-related/vaccinated cats or either whole blood or B-cell enriched population from MHC-unrelated cats were not protected. Given together, the dual-subtype FIV vaccine appears to induce complex immunity with FIV-specific CTL cytotoxin and Th cytokine responses. Homologous protection by adoptive transfer also appears to be mediated by T cells, associated with MHC, and occurred in the apparent absence of detectable B cells and antibodies. Cell-mediated immune activities with FIV-specific CTL and Th activity that supports both arms are generated by dual-subtype FIV vaccine and are additional protective mechanism of cats against homologous FIV. |
