Transcript CD8+ Memory T Cells Need Antigen-specific CD4+T

Antigen-specific CD4 T-Cell Help Is
Required to Activate a Memory CD8 T Cell
to a Fully Functional Tumor Killer Cell
高丰光
Background

CD8 mCTLs3 play a major role in the elimination
of viruses and tumors
 Before mCTLs can eliminate viruses and tumors,
these cells are required to roliferate and acquire
effector function.
 The role CD4 T-helper cells play in the induction
of CD8 effector T cells from naive precursors is
known
 the role of T-helper cells in the activation of
mCTLs when the antigen is presented by the
tumor is not established.
Question

How about T-helper cells in the activation
of memory T cells?
相关说明
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OT-1 mice : 表达SIINFEKL特异性TCR
OVA：鸡卵白蛋白
OVA CTL epitope: SIINFEKL
OVA Th epitope:ISQAVHAAHAEI-NEAGROVA （OVT）
RAG-1 KO mice:
C57BL/6 mice:
IFA/CFA/KLH
EG7 cell line
EL4 cell line
相关步骤
 mCTL and
eCTL generation
 specific Th generation
 mCTL transfer
 tumor challenge
OT-1 mice 的基本特征
mCTL generation
mCTL generation
mCTL generation
CTL+Th
CTL+KLH
CTL
Th
KLH
Control
1.0
0.8
0.6
0.4
Control
KLH
Th
CTL
0.0
CTL+KLH
0.2
CTL+Th
Tumour weight (g)
CD8+ Memory T Cells Need Antigen-specific CD4+T-helper
Cells to Achieve Tumor Protection
Absence of tumor protection in mice without antigen-specific
T-helper cells is not because of lower levels of tumor antigen
(SIINFEKL)-specific CD8+ T cells.
In contrast to mCTLs, eCTLs do not need T
help to kill tumor
Study of the long-lived memory CD8+ T
cells generated in C57BL/6J mice
1.Rowe HM, Lopes L, Ikeda Y, et al.
Immunization with a lentiviral vector stimulates both CD4 and CD8 T cell responses to an ovalbumin transgene
MOLECULAR THERAPY 13 (2): 310-319 FEB 2006
Times Cited: 0
2. Thompson JA, Dissanayake SK, Ksander BR, et al.
Tumor cells transduced with the MHC class II transactivator and CD80 activate tumor-specific CD4(+) T cells
whether or not they are silenced for invariant chain
CANCER RESEARCH 66 (2): 1147-1154 JAN 15 2006
Times Cited: 0
3. Salucci V, Mennuni C, Calvaruso F, et al.
CD8(+) T-cell tolerance can be broken by an adenoviral vaccine while CD4(+) T-cell tolerance is broken by
additional co-administration of a Toll-like receptor ligand
SCANDINAVIAN JOURNAL OF IMMUNOLOGY 63 (1): 35-41 JAN 2006
Times Cited: 0
4. Radford KJ, Vari F, Hart DNJ
Vaccine strategies to treat lymphoproliferative disorders
PATHOLOGY 37 (6): 534-550 DEC 2005
Times Cited: 1
5. Hu DE, Kettunen MI, Brindle KM
Monitoring T-lymphocyte trafficking in tumors undergoing immune rejection
MAGNETIC RESONANCE IN MEDICINE 54 (6): 1473-1479 DEC 2005
Times Cited: 0
6. Van Meirvenne S, Dullaers M, Heirman C, et al.
In vivo depletion of CD4(+)CD25(+) regulatory T cells enhances the antigen-specific primary and memory CTL
response elicited by mature mRNA-electroporated dendritic cells
MOLECULAR THERAPY 12 (5): 922-932 NOV 2005
Times Cited: 2
7. Miyazaki M, Nakatsura T, Yokomine K, et al.
DNA vaccination of HSP105 leads to tumor rejection of colorectal cancer and melanoma in mice through activation
of both CD4(+) T cells and CD8(+) T cells
CANCER SCIENCE 96 (10): 695-705 OCT 2005
Times Cited: 1
8.Kumaraguru U, Banerjee K, Rouse BT
In vivo rescue of defective memory CD8(+) T cells by cognate helper T cells
JOURNAL OF LEUKOCYTE BIOLOGY 78 (4): 879-887 OCT 2005
Times Cited: 0
9. Ostrand-Rosenberg S
CD4(+) T lymphocytes: A critical component of antitumor immunity
CANCER INVESTIGATION 23 (5): 413-419 2005
Times Cited: 2
10. Knutson KL, Disis ML
Tumor antigen-specific T helper cells in cancer immunity and immunotherapy
CANCER IMMUNOLOGY IMMUNOTHERAPY 54 (8): 721-728 AUG 2005
Times Cited: 4
11.Kutzler MA, Robinson TM, Chattergoon MA, et al.
Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially
independent of CD4 T cell help
JOURNAL OF IMMUNOLOGY 175 (1): 112-123 JUL 1 2005
Times Cited: 2
12. Meyer-Wentrup F, Richter G, Burdach S
Identification of an immunogenic EWS-FLI1-derived HLA-DR-restricted T helper cell epitope
PEDIATRIC HEMATOLOGY AND ONCOLOGY 22 (4): 297-308 JUN 2005
Times Cited: 0
13. Timar J, Ladanyi A, Forster-Horvath C, et al.
Neoadjuvant immunotherapy of oral squamous cell carcinoma modulates intratumoral CD4/CD8 ratio and tumor microenvironment:
A multicenter phase II clinical trial
JOURNAL OF CLINICAL ONCOLOGY 23 (15): 3421-3432 MAY 20 2005
Times Cited: 1
14. Tscharke DC, Suhrbier A
From mice to humans murine intelligence for human CD8(+) T cell vaccine design
EXPERT OPINION ON BIOLOGICAL THERAPY 5 (2): 263-271 FEB 2005
Times Cited: 1
15.Villada IB, Barracco MM, Ziol M, et al.
Spontaneous regression of grade 3 vulvar intraepithelial neoplasia associated with human papillomavirus-16-specific CD4(+) and
CD8(+) T-cell responses
CANCER RESEARCH 64 (23): 8761-8766 DEC 1 2004
Times Cited: 3
16. Altin JG, van Broekhoven CL, Parish CR
Targeting dendritic cells with antigen-containing liposomes: antitumour immunity
EXPERT OPINION ON BIOLOGICAL THERAPY 4 (11): 1735-1747 NOV 2004
Times Cited: 1
17. Leggatt GR, Narayan S, Fernando GJP, et al.
Changes to peptide structure, not concentration, contribute to expansion of the lowest avidity cytotoxic T lymphocytes
JOURNAL OF LEUKOCYTE BIOLOGY 76 (4): 787-795 OCT 2004
Times Cited: 0
18. Hsueh EC, Farnatiga E, Shu S, et al.
Peripheral blood CD4+ T-cell response before postoperative active immunotherapy correlates with clinical outcome in metastatic
melanoma
ANNALS OF SURGICAL ONCOLOGY 11 (10): 892-899 OCT 2004
Times Cited: 0
19. Hiraoka K, Yamamoto S, Otsuru S, et al.
Enhanced tumor-specific long-term immunity of hemaggluttinating virus of Japan-mediated dendritic cell-tumor fused cell vaccination-by
coadministration with CpG oligodeoxynucleotides
JOURNAL OF IMMUNOLOGY 173 (7): 4297-4307 OCT 1 2004
Times Cited: 1
20. Chiang EY, Stroynowski I
A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor
JOURNAL OF IMMUNOLOGY 173 (7): 4394-4401 OCT 1 2004
Times Cited: 3
21. Wong R, Lau R, Chang J, et al.
Immune responses to a class II helper peptide epitope in patients with stage III/IV resected melanoma
CLINICAL CANCER RESEARCH 10 (15): 5004-5013 AUG 1 2004
Times Cited: 6
22. Sun JB, Eriksson K, Li BL, et al.
Vaccination with dendritic cells pulsed in vitro with tumor antigen conjugated to cholera toxin efficiently induces specific turnoricidal CD8(+)
cytotoxic lymphocytes dependent on cyclic AMP activation of dendritic cells
CLINICAL IMMUNOLOGY 112 (1): 35-44 JUL 2004
Times Cited: 3
23. Zoller M
Immunotherapy of cancer for the elderly patient: does allogeneic bone marrow transplantation after nonmyeloablative conditioning
provide a new option?
CANCER IMMUNOLOGY IMMUNOTHERAPY 53 (8): 659-676 AUG 2004
Times Cited: 1
24. Chen QY, Jackson H, Parente P, et al.
Immunodominant CD4(+) responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 101 (25): 9363-9368 JUN 22 2004
Times Cited: 12
25. Nicholl M, Lodge A, Brown I, et al.
Restored immune response to an MHC-II-restricted antigen in tumor-bearing hosts after elimination of regulatory T cells
JOURNAL OF PEDIATRIC SURGERY 39 (6): 941-946 JUN 2004
Times Cited: 3
26. Shen L, Schroers R, Hammer J, et al.
Identification of a MHC class-II restricted epitope in carcinoembryonic antigen
CANCER IMMUNOLOGY IMMUNOTHERAPY 53 (5): 391-403 MAY 2004
Times Cited: 4
27.Ruiz M, Kobayashi H, Lasarte JJ, et al.
Identification and characterization of a T-helper peptide from carcinoembryonic antigen
CLINICAL CANCER RESEARCH 10 (8): 2860-2867 APR 15 2004
Times Cited: 2
28.Slager EH, van der Minne CE, Kruse M, et al.
Identification of multiple HLA-DR-restricted epitopes of the tumor-associated antigen CAMEL by CD4(+) Th1/Th2 lymphocytes
JOURNAL OF IMMUNOLOGY 172 (8): 5095-5102 APR 15 2004
Times Cited: 3
29. Johansen P, Stamou P, Tascon RE, et al.
CD4 T cells guarantee optimal competitive fitness of CD8 memory T cells
EUROPEAN JOURNAL OF IMMUNOLOGY 34 (1): 91-97 JAN 2004
Times Cited: 7
30. Frazer IH
Prevention of cervical cancer through papillomavirus vaccination
NATURE REVIEWS IMMUNOLOGY 4 (1): 46-54 JAN 2004
Times Cited: 37
31. Liu XS, Xu Y, Hardy L, et al.
IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral epitope in a primed host
JOURNAL OF IMMUNOLOGY 171 (9): 4765-4772 NOV 1 2003
Times Cited: 6
32. Nagorsen D, Scheibenbogen C, Marincola FM, et al.
Natural T cell immunity against cancer
CLINICAL CANCER RESEARCH 9 (12): 4296-4303 OCT 1 2003
Times Cited: 27
33. Tuyaerts S, Michiels A, Corthals J, et al.
Induction of Influenza Matrix Protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated
dendritic cells
CANCER GENE THERAPY 10 (9): 696-706 SEP 2003
Times Cited: 10
34.Finn OJ
Cancer vaccines: Between the idea and the reality
NATURE REVIEWS IMMUNOLOGY 3 (8): 630-641 AUG 2003
Times Cited: 108