Adoptive immunotherapy of feline immunodeficiency virus with autologous ex vivo-stimulated lymphoid cells modulates virus and T-cell subsets in blood.
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.
Flynn
J Norman
JN
Dipartimento di Patologia Sperimentale, Università di Pisa, Via San Zeno 37, I-56127 Pisa, Italy.
Pistello
Mauro
M
Isola
Patrizia
P
Zaccaro
Lucia
L
Del Santo
Barbara
B
Ricci
Enrica
E
Matteucci
Donatella
D
Bendinelli
Mauro
M
D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002371:Cat Diseases / Q000276:immunology* / Q000628:therapy / Q000821:virology; D002415:Cats; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D016180:Lentivirus Infections / Q000276:immunology* / Q000628:therapy / Q000662:veterinary; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D008562:Membrane Glycoproteins; D007371:Interferon-gamma