Reversal of feline leukemia virus infection by adoptive transfer of lectin/interleukin-2-activated lymphocytes, interferon-alpha, and zidovudine.
Previous experimental studies utilizing human recombinant interferon-alpha-2b (IFN alpha-2b) alone or with zidovudine (AZT) to treat established feline leukemia virus (FeLV) infection resulted in a significant reduction in circulating virus throughout a 49-day treatment period. However, the anti-FeLV effect of IFN alpha was limited by the production of IFN alpha-neutralizing antibodies detected 7 weeks after the start of treatment. AZT without IFN alpha had no effect on circulating virus load. To examine the hypothesis that combination chemoimmunotherapy might induce the clearance of FeLV infection, persistently infected cats were infused with activated lymphocytes, IFN alpha, and AZT 12 weeks after infection with FeLV. Recipient cats received weekly infusions of 1.46 x 10(8) lymphocytes activated in vitro with lectin/IL-2 comprised of 98% T cells and an even distribution of CD4+ and CD8+ lymphocytes. FeLV infection was cleared in 4 of 9 cats receiving combined therapy after four adoptive cell transfers. These cats remained negative for circulating virus during a 63-day treatment period (17 adoptive cell transfers) despite the production of anti-IFN alpha-neutralizing antibodies. Sequential development of virus-neutralizing and virus envelope antibody titers were detected in those cats which cleared retroviremia, an antiviral response that was absent in untreated control animals or nonresponders. Three of four responder cats remained negative for FeLV 95 days after treatment was discontinued. Treatment of cats with lymphocytes without chemotherapy failed to influence the course of FeLV infection. These results suggest that combined treatment using IFN alpha and adoptive lymphocyte transfer served to reconstitute antiviral humoral immunity, counteract immunosuppression, and induce the reversal of retroviremia.
Zeidner
N S
NS
Department of Pathology, Colorado State University, Fort Collins 80523.
Mathiason-DuBard
C K
CK
Hoover
E A
EA
D000818:Animals; D000917:Antibody Formation; D002415:Cats; D003131:Combined Modality Therapy; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000494:pharmacology; D005256:Leukemia Virus, Feline; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D009500:Neutralization Tests; D010641:Phenotype; D011994:Recombinant Proteins; D014766:Viremia / Q000188:drug therapy / Q000628:therapy; D015215:Zidovudine / Q000008:administration & dosage
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A; D015215:Zidovudine