RGD Reference Report - Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes. - Rat Genome Database

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Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes.

Authors: Lohmann, T  Laue, S  Nietzschmann, U  Kapellen, TM  Lehmann, I  Schroeder, S  Paschke, R  Kiess, W 
Citation: Lohmann T, etal., Diabetes. 2002 Aug;51(8):2474-80.
RGD ID: 2317571
Pubmed: PMID:12145160   (View Abstract at PubMed)

We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. The patients with newly diagnosed type 1 diabetes were followed for these parameters at 6-12 months after diagnosis. The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. We assume that Th1-associated peripheral T-cells are reduced in a narrow time window at the time of diagnosis of diabetes, possibly due to extravasation in the inflamed pancreas. Thus, chemokine receptor expression of peripheral blood lymphocytes may be a useful surrogate marker for the immune activity of type 1 diabetes (e.g., in intervention trials).



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCR5Humantype 1 diabetes mellitus  IEP protein:decreased expression:blood and mononuclear cellRGD 
Ccr5Rattype 1 diabetes mellitus  ISOCCR5 (Homo sapiens)protein:decreased expression:blood and mononuclear cellRGD 
Ccr5Mousetype 1 diabetes mellitus  ISOCCR5 (Homo sapiens)protein:decreased expression:blood and mononuclear cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Mus musculus)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Homo sapiens)
CCR5  (C-C motif chemokine receptor 5)


Additional Information