PMID- 18817831
OWN - NLM
STAT- MEDLINE
DCOM- 20090123
LR  - 20201214
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 69
IP  - 11
DP  - 2008 Nov
TI  - Human leukocyte antigen class I-restricted immunosuppression by human CD8+ 
      regulatory T cells requires CTLA-4-mediated interaction with dendritic cells.
PG  - 687-95
LID - 10.1016/j.humimm.2008.08.277 [doi]
AB  - We previously reported autoreactive CD8(+) regulatory T cells (Tregs) that were 
      expanded and cloned from human peripheral blood by coculture with autologous 
      dendritic cells (DC). Here we demonstrate that these CD8(+) Tregs require human 
      leukocyte antigen (HLA)-class I restricted activation and then mediate 
      cell-contact-dependent suppression of CD4(+) T cells. CD8(+) Tregs interacted 
      with DC to suppress T-cell responses but DC were not irreversibly altered by this 
      interaction because they could subsequently stimulate CD4(+) T cells normally. 
      The ability of DC to form conjugates with CD4(+) T cells was reduced in the 
      presence of CD8(+) Tregs. Suppression was blocked by Abs to CD80 and CTLA-4, 
      implicating CTLA-4:CD80 interactions in the function of CD8(+) Tregs. CD8(+) 
      Tregs rapidly express very high levels of surface CTLA-4 following activation 
      compared with conventional T cells. Related to this, the expression of TRAT1 mRNA 
      (T-cell receptor interacting molecule, or TRIM) was highly upregulated in 
      microarray analysis of CD8(+) Tregs compared with conventional cytotoxic or 
      nonregulatory CD8(+) T cells. TRIM acts to chaperone CTLA-4 transport to the cell 
      surface; this function would be required to account for the phenotypic and 
      functional properties of CD8(+) Tregs.
FAU - Jarvis, Lorna B
AU  - Jarvis LB
AD  - Department of Rheumatology, University of Cambridge, Cambridge, UK.
FAU - Goodall, Jane C
AU  - Goodall JC
FAU - Gaston, J S Hill
AU  - Gaston JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080924
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antibodies)
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TRAT1 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/biosynthesis/immunology
MH  - Antibodies/pharmacology
MH  - Antigens, CD/biosynthesis/*immunology
MH  - B7-1 Antigen/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - CTLA-4 Antigen
MH  - Cell Communication/drug effects/*immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Gene Expression Profiling
MH  - Histocompatibility Antigens Class I/biosynthesis/*immunology
MH  - Humans
MH  - Immune Tolerance/drug effects/*physiology
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Membrane Proteins/biosynthesis/immunology
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/biosynthesis/immunology
MH  - Up-Regulation/drug effects/immunology
EDAT- 2008/09/27 09:00
MHDA- 2009/01/24 09:00
CRDT- 2008/09/27 09:00
PHST- 2008/07/17 00:00 [received]
PHST- 2008/08/11 00:00 [revised]
PHST- 2008/08/12 00:00 [accepted]
PHST- 2008/09/27 09:00 [pubmed]
PHST- 2009/01/24 09:00 [medline]
PHST- 2008/09/27 09:00 [entrez]
AID - S0198-8859(08)00437-0 [pii]
AID - 10.1016/j.humimm.2008.08.277 [doi]
PST - ppublish
SO  - Hum Immunol. 2008 Nov;69(11):687-95. doi: 10.1016/j.humimm.2008.08.277. Epub 2008 
      Sep 24.