title: CD4+ T lymphocytes are critical mediators of tumor immunity to simian virus 40 large tumor antigen induced by vaccination with plasmid DNA.
abstract: A mechanistic analysis of tumor immunity directed toward the viral oncoprotein simian virus 40 (SV40) large tumor antigen (Tag) has previously been described by our laboratory for scenarios of recombinant Tag immunization in BALB/c mice. In the present study, we performed a preliminary characterization of the immune components necessary for systemic tumor immunity induced upon immunization with plasmid DNA encoding SV40 Tag as a transgene (pCMV-Tag). Antibody responses to SV40 Tag were observed via indirect enzyme-linked immunosorbent assay following three intramuscular (i.m.) injections of pCMV-Tag and were typified by a mixed Th1/Th2 response. Complete tumor immunity within a murine model of pulmonary metastasis was achieved upon two i.m. injections of pCMV-Tag, as assessed by examination of tumor foci in mouse lungs, without a detectable antibody response to SV40 Tag. Induction-phase and effector-phase depletions of T cell subsets were performed in vivo via administration of depleting rat monoclonal antibodies, and these experiments demonstrated that CD4(+) T lymphocytes are required in both phases of the adaptive immune response. Conversely, depletion of CD8(+) T lymphocytes did not impair tumor immunity in either immune phase and resulted in the premature production of antibodies to SV40 Tag. Our findings are unique in that a dominant role could be ascribed to CD4(+) T lymphocytes within a model of DNA vaccine-induced tumor immunity to Tag-expressing tumor cells. Additionally, our findings provide insight into the general mechanisms of vaccine-induced tumor immunity directed toward tumors bearing distinct tumor-associated antigens.
authors: Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6591, Lubbock, TX 79430, USA.
authors: Joel F
authors: JF
authors: Aldrich
authors: Devin B
authors: DB
authors: Lowe
authors: Michael H
authors: MH
authors: Shearer
authors: Richard E
authors: RE
authors: Winn
authors: Cynthia A
authors: CA
authors: Jumper
authors: Robert K
authors: RK
authors: Bright
authors: Ronald C
authors: RC
authors: Kennedy
references: Biol Chem. 2001 Apr;382(4):543-52
references: 11405219
references: Immunotherapy. 2011 Jan;3(1):27-31
references: 21174555
references: Virology. 1998 May 10;244(2):427-41
references: 9601511
references: J Immunol. 1980 Apr;124(4):1888-91
references: 6154083
references: Cancer Res. 2003 Mar 1;63(5):1040-5
references: 12615720
references: Cancer Immunol Immunother. 2004 Nov;53(11):987-94
references: 15156293
references: Curr Oncol Rep. 2011 Apr;13(2):112-9
references: 21243538
references: Infect Immun. 2006 May;74(5):2751-9
references: 16622212
references: Cell Immunol. 1991 Oct 15;137(2):474-86
references: 1832587
references: Nat Med. 1996 Aug;2(8):893-8
references: 8705859
references: Immunity. 2000 Jun;12(6):677-86
references: 10894167
references: J Virol. 2010 Oct;84(19):10121-30
references: 20668083
references: Nat Rev Immunol. 2006 May;6(5):343-57
references: 16622479
references: J Virol. 2007 Feb;81(3):1313-8
references: 17108042
references: Endocrinology. 2007 Dec;148(12):6040-6
references: 17823258
references: Cancer Immunol Immunother. 1999 Feb;47(6):343-51
references: 10203065
references: Clin Cancer Res. 2006 Apr 1;12(7 Pt 2):2353s-2358s
references: 16609058
references: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10214-9
references: 10954737
references: Cancer Gene Ther. 2010 Oct;17(10):708-20
references: 20539319
references: Proc Soc Exp Biol Med. 1962 Mar;109:649-60
references: 13898881
references: Proc Soc Exp Biol Med. 1961 May;107:191-7
references: 13725644
references: Immunol Rev. 1995 Aug;146:57-79
references: 7493761
references: Blood. 2007 Jun 15;109(12):5346-54
references: 17327412
references: Cancer Res. 1996 Mar 1;56(5):1126-30
references: 8640771
references: Cell Mol Life Sci. 2007 Apr;64(7-8):803-14
references: 17260087
references: Cancer. 2009 May 15;115(10 Suppl):2298-305
references: 19402060
references: J Virol. 2010 Jan;84(2):883-93
references: 19889780
references: Am J Med. 2003 Jun 1;114(8):675-84
references: 12798456
references: Virology. 1997 Feb 17;228(2):278-84
references: 9123835
references: Nature. 1988 Jul 21;334(6179):255-8
references: 2456466
references: Gene Ther. 2006 Feb;13(3):257-65
references: 16177818
references: Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8726-31
references: 9238045
references: Int Rev Immunol. 2003 Mar-Apr;22(2):113-40
references: 12962272
references: Virology. 2005 Feb 5;332(1):28-37
references: 15661138
references: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8633-8
references: 10411927
references: Viral Immunol. 2006 Summer;19(3):492-507
references: 16987067
references: Cancer Invest. 2005;23(5):413-9
references: 16193641
references: Semin Cancer Biol. 1999 Dec;9(6):431-44
references: 10712890
references: J Virol Methods. 1997 Dec;69(1-2):93-102
references: 9504755
references: Eur J Immunol. 2000 Sep;30(9):2455-9
references: 11009076
references: Clin Genitourin Cancer. 2010 Dec 1;8(1):10-6
references: 21208850
references: Immunity. 2005 Jul;23(1):41-51
references: 16039578
references: Expert Rev Anticancer Ther. 2011 Jan;11(1):25-8
references: 21166508
references: Nat Rev Immunol. 2010 Aug;10(8):580-93
references: 20651745
references: J Immunol. 1991 Nov 15;147(10):3370-80
references: 1834737
references: J Virol. 2003 May;77(9):5039-45
references: 12692206
references: Immunity. 2006 Jan;24(1):19-28
references: 16413920
references: Immunol Rev. 2008 Apr;222:129-44
references: 18363998
references: Vaccine. 1997 Jun;15(8):795-7
references: 9234516
references: Nature. 1962 Jul 21;195:299-300
references: 14456349
references: Clin Dev Immunol. 2010;2010:697158
references: 20936120
references: Cell Mol Life Sci. 2007 Sep;64(18):2391-403
references: 17565444