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Adoptive Immunotherapy of Feline Immunodeficiency Virus with Autologous Ex Vivo-Stimulated Lymphoid Cells Modulates Virus and T-Cell Subsets in Blood

Retrovirus Center, Department of Experimental Pathology, University of Pisa, Pisa, Italy,¹ Institute of Comparative Medicine, Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow, Glasgow, United Kingdom²

Received 2 December 2004/ Returned for modification 22 February 2005/ Accepted 16 March 2005

The potential of immunotherapy with autologous virus-specific T cells to affect the course of feline immunodeficiency virus (FIV) infection was explored in a group of specific-pathogen-free cats infected with FIV a minimum of 10 months earlier. Popliteal lymph node cells were stimulated by cocultivation with UV-inactivated autologous fibroblasts infected with recombinant vaccinia viruses expressing either FIV gag or env gene products, followed by expansion in interleukin-2. One or two infusions of both Gag- and Env-stimulated cells resulted in a slow increase in FIV-specific gamma interferon-secreting T cells in the circulation of cats. In the same animals, viral set points fluctuated widely during the first 2 to 3 weeks after adoptive transfer and then returned to pretreatment levels. The preexisting viral quasispecies was also found to be modulated, whereas no novel viral variants were detected. Circulating CD4⁺ counts underwent a dramatic decline early after treatment. CD4/CD8 ratios remained instead essentially unchanged and eventually improved in some animals. In contrast, a single infusion of Gag-stimulated cells alone produced no apparent modulations of infection.