Islet inflammation and CXCL10 in recent-onset type 1 diabetes

B. O. Roep, F. S. Kleijwegt, A. G.S. Van Halteren, V. Bonato, U. Boggi, F. Vendrame, P. Marchetti, F. Dotta

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

Type 1 diabetes results from a T cell-mediated destruction of insulin-producing pancreatic β cells. Little is known on local factors contributing to migration of T cells to pancreatic tissue. We recently demonstrated evidence of viral infection in β cells in several recent-onset type 1 diabetes patients. Islet inflammation was analysed in a series of new- or recent-onset type 1 diabetic patients and non-diabetic control subjects. Autoimmune T cell reactivity was studied in lymphocytes derived from pancreas-draining lymph nodes of one recent-onset type 1 diabetes patient in partial clinical remission. Insulitic lesions were characterized by presence of β cells, elevated levels of the chemokine CXCL10 and infiltration of lymphocytes expressing the corresponding chemokine receptor CXCR3 in all pancreatic lesions of type 1 diabetes patients, regardless of enterovirus infection of β cells. CXCR3 and CXCL10 were undetectable in pancreata of non-diabetic control subjects. T cells isolated from draining lymph nodes of a recent-onset patient with virally infected β cells and in clinical remission reacted with multiple islet autoantigens and displayed a mixed interferon (IFN)-γ/interleukin (IL)-10 cytokine pattern. Our data point to CXCL10 as an important cytokine in distressed islets that may contribute to inflammation leading to insulitis and β cell destruction, regardless of local viral infection. We demonstrate further pro- and anti-inflammatory islet autoreactivity, indicating that different adaptive and innate immune responses may contribute to insulitis and β cell destruction.

Original languageEnglish (US)
Pages (from-to)338-343
Number of pages6
JournalClinical and Experimental Immunology
Volume159
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Autoreactive T cells
  • CXCL10
  • CXCR3
  • IP-10
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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