HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lohmann, T. Articles by Kiess, W. Search for Related Content PubMed PubMed Citation Articles by Lohmann, T. Articles by Kiess, W. Social Bookmarking                What's this?

Reduced Expression of Th1-Associated Chemokine Receptors on Peripheral Blood Lymphocytes at Diagnosis of Type 1 Diabetes

¹ Department of Internal Medicine III, University of Leipzig, Leipzig, Germany
² Childrens Hospital, University of Leipzig, Leipzig, Germany
³ Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany

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]-1, MIP-1ß, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (-interferon [IFN-] and tumor necrosis factor- [TNF-]) 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- and TNF- 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-1 and MIP-1ß 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).

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				C. Meagher, G. Arreaza, A. Peters, C. A. Strathdee, P. A. Gilbert, Q.-S. Mi, P. Santamaria, G. A. Dekaban, and T. L. Delovitch CCL4 Protects From Type 1 Diabetes by Altering Islet {beta}-Cell-Targeted Inflammatory Responses Diabetes, March 1, 2007; 56(3): 809 - 817. [Abstract] [Full Text] [PDF]

				S. Skarsvik, J. Puranen, J. Honkanen, M. Roivainen, J. Ilonen, H. Holmberg, J. Ludvigsson, and O. Vaarala Decreased in vitro type 1 immune response against coxsackie virus b4 in children with type 1 diabetes. Diabetes, April 1, 2006; 55(4): 996 - 1003. [Abstract] [Full Text] [PDF]

				D. Chen, N. Zhang, S. Fu, B. Schroppel, Q. Guo, A. Garin, S. A. Lira, and J. S. Bromberg CD4+CD25+ Regulatory T-Cells Inhibit the Islet Innate Immune Response and Promote Islet Engraftment. Diabetes, April 1, 2006; 55(4): 1011 - 1021. [Abstract] [Full Text] [PDF]

				R. Pyo, K. K. Jensen, M. T. Wiekowski, D. Manfra, A. Alcami, M. B. Taubman, and S. A. Lira Inhibition of Intimal Hyperplasia in Transgenic Mice Conditionally Expressing the Chemokine-Binding Protein M3 Am. J. Pathol., June 1, 2004; 164(6): 2289 - 2297. [Abstract] [Full Text] [PDF]

				W. Iijima, H. Ohtani, T. Nakayama, Y. Sugawara, E. Sato, H. Nagura, O. Yoshie, and T. Sasano Infiltrating CD8+ T Cells in Oral Lichen Planus Predominantly Express CCR5 and CXCR3 and Carry Respective Chemokine Ligands RANTES/CCL5 and IP-10/CXCL10 in Their Cytolytic Granules: A Potential Self-Recruiting Mechanism Am. J. Pathol., July 1, 2003; 163(1): 261 - 268. [Abstract] [Full Text] [PDF]