PMID- 16956670
OWN - NLM
STAT- MEDLINE
DCOM- 20070205
LR  - 20181201
IS  - 0165-2478 (Print)
IS  - 0165-2478 (Linking)
VI  - 107
IP  - 2
DP  - 2006 Nov 15
TI  - Reduced cytokine-mediated up-regulation of HLA-DR in TAP-deficient fibroblasts.
PG  - 109-18
AB  - Human deficiency in transporter associated with antigen processing (TAP) is 
      characterized by a very low surface expression of human leukocyte antigen (HLA) 
      class I molecules in hematopoietic and non hematopoietic cells. Among the latter, 
      TAP-deficient skin fibroblasts have previously been shown by us to be very 
      sensitive to lysis by activated autologous NK cells, even in the presence of 
      cytokines that up-regulate HLA class I expression, a mechanism sufficient to 
      protect normal fibroblasts from NK cell-mediated killing. Our complementary 
      investigations on two TAP-deficient skin fibroblast cell lines surprisingly 
      revealed that in response to proinflammatory cytokines, up-regulation of HLA-DR 
      molecules at the cell surface is much less marked than in the case of normal skin 
      fibroblasts. In contrast, the surface molecules CD40 and CD54 increase as much as 
      observed on normal cells, suggesting that TAP-deficient fibroblasts are able to 
      efficiently transduce cytokine-mediated stimulating signals. Transfection of an 
      intact TAP gene into one of the TAP-deficient fibroblast cell lines restored a 
      normal HLA class I expression that strongly increased upon IFN-gamma-mediated 
      stimulation, whereas HLA-DR still remained lower than in control cells. These 
      results suggest that, in addition to the defect in the HLA class I antigen 
      presentation pathway, HLA-DR up-regulation is affected in TAP-deficient skin 
      fibroblasts through an unknown mechanism probably independent from TAP.
FAU - Zimmer, Jacques
AU  - Zimmer J
AD  - Laboratoire d'Immunogenetique-Allergologie, Centre de Recherche Public de la 
      Sante (CRP-Sante), 84 Val Fleuri, L-1526 Luxembourg, Luxembourg. 
      jacques.zimmer@crp-sante.lu
FAU - Poli, Aurelie
AU  - Poli A
FAU - Andres, Emmanuel
AU  - Andres E
FAU - Hanau, Daniel
AU  - Hanau D
FAU - Brons, Nicolaas H C
AU  - Brons NH
FAU - Hentges, Francois
AU  - Hentges F
LA  - eng
PT  - Journal Article
DEP - 20060822
PL  - Netherlands
TA  - Immunol Lett
JT  - Immunology letters
JID - 7910006
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 3)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (CD40 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (TAP1 protein, human)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 145892-13-3 (TAP2 protein, human)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 3
MH  - ATP-Binding Cassette Transporters/genetics/*metabolism
MH  - CD40 Antigens/metabolism
MH  - Cells, Cultured
MH  - Cytokines/*metabolism/pharmacology
MH  - Fibroblasts/drug effects/immunology
MH  - HLA-DR Antigens/*metabolism
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interferon-gamma/pharmacology
MH  - Skin/cytology/drug effects/*immunology
MH  - Transfection
MH  - Up-Regulation
EDAT- 2006/09/08 09:00
MHDA- 2007/02/06 09:00
CRDT- 2006/09/08 09:00
PHST- 2005/12/19 00:00 [received]
PHST- 2006/07/31 00:00 [revised]
PHST- 2006/07/31 00:00 [accepted]
PHST- 2006/09/08 09:00 [pubmed]
PHST- 2007/02/06 09:00 [medline]
PHST- 2006/09/08 09:00 [entrez]
AID - S0165-2478(06)00203-3 [pii]
AID - 10.1016/j.imlet.2006.07.010 [doi]
PST - ppublish
SO  - Immunol Lett. 2006 Nov 15;107(2):109-18. doi: 10.1016/j.imlet.2006.07.010. Epub 
      2006 Aug 22.