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Clinical and Diagnostic Laboratory Immunology, June 2005, p. 736-745, Vol. 12, No. 6
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.6.736-745.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

J. Norman Flynn,1,2 Mauro Pistello,1 Patrizia Isola,1 Lucia Zaccaro,1 Barbara Del Santo,1 Enrica Ricci,1 Donatella Matteucci,1 and Mauro Bendinelli1*

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.


* Corresponding author. Mailing address: Dipartimento di Patologia Sperimentale, Università di Pisa, Via San Zeno 37, I-56127 Pisa, Italy. Phone: 39-050-2213-641. Fax: 39-050-2213-639. E-mail: bendinelli{at}biomed.unipi.it.


Clinical and Diagnostic Laboratory Immunology, June 2005, p. 736-745, Vol. 12, No. 6
1071-412X/05/$08.00+0     doi:10.1128/CDLI.12.6.736-745.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.







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