PMID- 10072490
OWN - NLM
STAT- MEDLINE
DCOM- 19990414
LR  - 20071114
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 5
DP  - 1999 Mar 1
TI  - Islet-specific Th1, but not Th2, cells secrete multiple chemokines and promote 
      rapid induction of autoimmune diabetes.
PG  - 2511-20
AB  - Migration of CD4 cells into the pancreas represents a hallmark event in the 
      development of insulin-dependent diabetes mellitus. Th1, but not Th2, cells are 
      associated with pathogenesis leading to destruction of islet beta-cells and 
      disease onset. Lymphocyte extravasation from blood into tissue is regulated by 
      multiple adhesion receptor/counter-receptor pairs and chemokines. To identify 
      events that regulate entry of CD4 cells into the pancreas, we transferred Th1 or 
      Th2 cells induced in vitro from islet-specific TCR transgenic CD4 cells into 
      immunodeficient (NOD.scid) recipients. Although both subsets infiltrated the 
      pancreas and elicited multiple adhesion receptors (peripheral lymph node 
      addressin, mucosal addressin cell adhesion molecule-1, LFA-1, ICAM-1, and VCAM-1) 
      on vascular endothelium, entry/accumulation of Th1 cells was more rapid than that 
      of Th2 cells, and only Th1 cells induced diabetes. In vitro, Th1 cells were also 
      distinguished from Th2 cells by the capacity to synthesize several chemokines 
      that included lymphotactin, monocyte chemoattractant protein-1 (MCP-1), and 
      macrophage inflammatory protein-1alpha, whereas both subsets produced macrophage 
      inflammatory protein-1beta. Some of these chemokines as well as RANTES, MCP-3, 
      MCP-5, and cytokine-response gene-2 (CRG-2)/IFN-inducible protein-10 (IP-10) were 
      associated with Th1, but not Th2, pancreatic infiltrates. The data demonstrate 
      polarization of chemokine expression by Th1 vs Th2 cells, which, within the 
      microenvironment of the pancreas, accounts for distinctive inflammatory 
      infiltrates that determine whether insulin-producing beta-cells are protected or 
      destroyed.
FAU - Bradley, L M
AU  - Bradley LM
AD  - Departments ofImmunology and Neuropharmacology, The Scripps Research Institute, 
      La Jolla, CA 92037, USA. lbradley@scripps.edu
FAU - Asensio, V C
AU  - Asensio VC
FAU - Schioetz, L K
AU  - Schioetz LK
FAU - Harbertson, J
AU  - Harbertson J
FAU - Krahl, T
AU  - Krahl T
FAU - Patstone, G
AU  - Patstone G
FAU - Woolf, N
AU  - Woolf N
FAU - Campbell, I L
AU  - Campbell IL
FAU - Sarvetnick, N
AU  - Sarvetnick N
LA  - eng
GR  - AI37935/AI/NIAID NIH HHS/United States
GR  - HD29764/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokines)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
SB  - IM
MH  - Animals
MH  - Chemokines/*physiology
MH  - Diabetes Mellitus, Type 1/*etiology
MH  - Female
MH  - Islets of Langerhans/*immunology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Transgenic
MH  - Receptors, Antigen, T-Cell, alpha-beta/analysis
MH  - Th1 Cells/*immunology
MH  - Th2 Cells/*immunology
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Mar 1;162(5):2511-20.