PMID- 15728465
OWN - NLM
STAT- MEDLINE
DCOM- 20050419
LR  - 20210102
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 174
IP  - 5
DP  - 2005 Mar 1
TI  - CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper 
      cells and hindered by naturally occurring T regulatory cells.
PG  - 2591-601
AB  - CD4(+) T cells control the effector function, memory, and maintenance of CD8(+) T 
      cells. Paradoxically, we found that absence of CD4(+) T cells enhanced adoptive 
      immunotherapy of cancer when using CD8(+) T cells directed against a persisting 
      tumor/self-Ag. However, adoptive transfer of CD4(+)CD25(-) Th cells (Th cells) 
      with tumor/self-reactive CD8(+) T cells and vaccination into CD4(+) T 
      cell-deficient hosts induced autoimmunity and regression of established melanoma. 
      Transfer of CD4(+) T cells that contained a mixture of Th and CD4(+)CD25(+) T 
      regulatory cells (T(reg) cells) or T(reg) cells alone prevented effective 
      adoptive immunotherapy. Maintenance of CD8(+) T cell numbers and function was 
      dependent on Th cells that were capable of IL-2 production because therapy failed 
      when Th cells were derived from IL-2(-/-) mice. These findings reveal that Th 
      cells can help break tolerance to a persisting self-Ag and treat established 
      tumors through an IL-2-dependent mechanism, but requires simultaneous absence of 
      naturally occurring T(reg) cells to be effective.
FAU - Antony, Paul A
AU  - Antony PA
AD  - Division of Surgery, Center for Cancer Research, National Cancer Institute, 
      National Institutes of Health, Bethesda, MD 20892, USA. Paul.Antony@nih.gov
FAU - Piccirillo, Ciriaco A
AU  - Piccirillo CA
FAU - Akpinarli, Akgul
AU  - Akpinarli A
FAU - Finkelstein, Steven E
AU  - Finkelstein SE
FAU - Speiss, Paul J
AU  - Speiss PJ
FAU - Surman, Deborah R
AU  - Surman DR
FAU - Palmer, Douglas C
AU  - Palmer DC
FAU - Chan, Chi-Chao
AU  - Chan CC
FAU - Klebanoff, Christopher A
AU  - Klebanoff CA
FAU - Overwijk, Willem W
AU  - Overwijk WW
FAU - Rosenberg, Steven A
AU  - Rosenberg SA
FAU - Restifo, Nicholas P
AU  - Restifo NP
LA  - eng
GR  - Z01 BC010763-01/Intramural NIH HHS/United States
GR  - Z01 SC003811-32/Intramural NIH HHS/United States
GR  - Z99 CA999999/Intramural NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Interleukin-2)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Pmel protein, mouse)
RN  - 0 (Receptors, Interleukin-2)
RN  - 0 (gp100 Melanoma Antigen)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology/*transplantation
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Proliferation
MH  - Homeostasis/immunology
MH  - Immunity, Innate
MH  - *Immunotherapy, Adoptive/adverse effects/methods
MH  - Interleukin-2/physiology/therapeutic use
MH  - Lymphocyte Activation/immunology
MH  - Melanoma, Experimental/*immunology/pathology/therapy
MH  - Membrane Glycoproteins/biosynthesis/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/biosynthesis/*immunology
MH  - Receptors, Interleukin-2/biosynthesis
MH  - Self Tolerance/*immunology
MH  - T-Lymphocytes, Regulatory/immunology/*transplantation
MH  - Transplantation Tolerance/immunology
MH  - Tumor Escape/immunology
MH  - gp100 Melanoma Antigen
PMC - PMC1403291
MID - NIHMS6258
EDAT- 2005/02/25 09:00
MHDA- 2005/04/20 09:00
PMCR- 2008/02/01
CRDT- 2005/02/25 09:00
PHST- 2005/02/25 09:00 [pubmed]
PHST- 2005/04/20 09:00 [medline]
PHST- 2005/02/25 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - 174/5/2591 [pii]
AID - 10.4049/jimmunol.174.5.2591 [doi]
PST - ppublish
SO  - J Immunol. 2005 Mar 1;174(5):2591-601. doi: 10.4049/jimmunol.174.5.2591.