PMID- 11777993
OWN - NLM
STAT- MEDLINE
DCOM- 20020131
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 168
IP  - 2
DP  - 2002 Jan 15
TI  - Igs from patients with Graves' disease induce the expression of T cell 
      chemoattractants in their fibroblasts.
PG  - 942-50
AB  - Thyroid-associated ophthalmopathy and dermopathy are connective tissue 
      manifestations of Graves' disease (GD). Tissue remodeling is a prominent feature 
      of both and is apparently driven by recruited T cells. In this study, we report 
      that IgG isolated from patients with GD (GD-IgG) up-regulates T lymphocyte 
      chemoattractant activity in GD-derived fibroblasts from orbit, thyroid, and 
      several regions of skin. This chemoattractant activity, absent in fibroblasts 
      from donors without known thyroid disease, is partially susceptible to 
      neutralization by anti-IL-16 and anti-RANTES Abs. IL-16 is a CD4(+)-specific 
      chemoattractant and RANTES is a C-C-type chemokine. IL-16 and RANTES protein 
      levels, as determined by specific ELISAs, are substantially increased by GD-IgG 
      in GD fibroblasts. Addition of the macrolide, rapamycin, to fibroblast culture 
      medium blocked the up-regulation by GD-IgG of IL-16, implicating the 
      FRAP/mTOR/p70(s6k) pathway in the induction of IL-16 expression. These findings 
      suggest a specific mechanism for activation of fibroblasts in GD resulting in the 
      recruitment of T cells. They may provide insight into a missing link between the 
      glandular and extrathyroidal manifestations of GD.
FAU - Pritchard, Jane
AU  - Pritchard J
AD  - Department of Medicine, Division of Molecular Medicine, Harbor-University of 
      California, Los Angeles Medical Center, Torrance, CA 90502, USA.
FAU - Horst, Noah
AU  - Horst N
FAU - Cruikshank, William
AU  - Cruikshank W
FAU - Smith, Terry J
AU  - Smith TJ
LA  - eng
GR  - EY011708/EY/NEI NIH HHS/United States
GR  - EY08976/EY/NEI NIH HHS/United States
GR  - HL32802/HL/NHLBI NIH HHS/United States
GR  - M01 RR00425/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Immune Sera)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-16)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL5/biosynthesis
MH  - Chemotactic Factors/*biosynthesis/metabolism
MH  - Chemotaxis, Leukocyte/immunology
MH  - Fibroblasts/enzymology/*immunology/*metabolism
MH  - Graves Disease/*immunology
MH  - Humans
MH  - Immune Sera/pharmacology
MH  - Immunoglobulin G/*pharmacology
MH  - Immunosuppressive Agents/pharmacology
MH  - Interleukin-16/antagonists & inhibitors/biosynthesis/metabolism
MH  - Signal Transduction/drug effects/immunology
MH  - Sirolimus/pharmacology
MH  - T-Lymphocytes/*immunology
EDAT- 2002/01/05 10:00
MHDA- 2002/02/01 10:01
CRDT- 2002/01/05 10:00
PHST- 2002/01/05 10:00 [pubmed]
PHST- 2002/02/01 10:01 [medline]
PHST- 2002/01/05 10:00 [entrez]
AID - 10.4049/jimmunol.168.2.942 [doi]
PST - ppublish
SO  - J Immunol. 2002 Jan 15;168(2):942-50. doi: 10.4049/jimmunol.168.2.942.