Research Article

Identical twins discordant for type 1 diabetes show a different pattern of in vitro CD56+ cell activation

  1. Martin R. Goodier1,*,
  2. Niga Nawroly2,
  3. Huriya Beyan3,
  4. Mohammed Hawa3,
  5. R. David G. Leslie3,
  6. Marco Londei4

Article first published online: 30 MAR 2006

DOI: 10.1002/dmrr.627

Issue

Diabetes/Metabolism Research and Reviews

Diabetes/Metabolism Research and Reviews

Volume 22, Issue 5, pages 367–375, September 2006

Additional Information

How to Cite

Goodier, M. R., Nawroly, N., Beyan, H., Hawa, M., Leslie, R. D. G. and Londei, M. (2006), Identical twins discordant for type 1 diabetes show a different pattern of in vitro CD56+ cell activation. Diabetes/Metabolism Research and Reviews, 22: 367–375. doi: 10.1002/dmrr.627

Author Information

  1. 1

    Department of Immunology Imperial College London, Faculty of Medicine, Chelsea and Westminster Hospital, UK

  2. 2

    National Heart and Lung Institute, Imperial College London, Faculty of Medicine, St Marys Campus, London, UK

  3. 3

    Diabetes and Immunology Unit, St Bartholomews Hospital, Queen Mary College, London, UK

  4. 4

    Academic Unit of Gastroenterology and Autoimmunity, Institute of Child Health, University College London, UK

*Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road London, SW10 9NH, UK.

Publication History

  1. Issue published online: 26 AUG 2006
  2. Article first published online: 30 MAR 2006
  3. Manuscript Accepted: 26 DEC 2005
  4. Manuscript Revised: 19 DEC 2005
  5. Manuscript Received: 6 JUL 2005

Funded by

  • European Community Grant. Grant Number: QLK1-CT-1999-00037
  • Arthritis Research Campaign, UK
  • The Wellcome Trust Grant. Grant Number: 050453
  • Juvenile Diabetes Research Foundation International and Diabetes UK

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Keywords:

  • NK cells;
  • diabetes;
  • human

Abstract

Background

Recent studies in animal models indicate a role for natural killer (NK) cells in the protection against type 1 diabetes. In humans, a reduction of NK cell numbers has been reported in identical twins discordant for type 1 diabetes, irrespective of whether they have the disease. Here we have tested whether the activation and expansion of human NK cells with lipopolysaccharide (LPS) reveals differences between these twins.

Methods

Proportions of CD56+ NK cells and T-cells and Va24Vb11+ NK-T cells from diabetic and non-diabetic twins was assessed before and after activation using flow cytometry. NK receptor usage was monitored by PCR and flow cytometry.

Results

The profile of the expressed Killer Cell immunoglobulin-like receptor (KIR) repertoire (using mRNA) in freshly isolated NK cells was identical in pairs of identical twins, despite marked variation among individual twins as well as controls. Basal numbers of CD56+ and CD94+ (CD3− and CD3+) cells and Vα24+Vβ11+ NK-T cells were similarly strongly correlated between identical twins (p < 0.006 for all correlations). Following LPS stimulation, the pattern of KIR mRNA expression remained unaltered in twins and the proportion of NK cells and Vα24+Vβ11+ NK-T cells remained correlated between pairs of twins. However, there was a significant reduction in the proportion of CD56+ cells and CD94+ cells (whether defined as CD3− or CD3+) responding to LPS in the diabetic compared to the non-diabetic twin (p = 0.031 and 0.025, respectively).

Conclusion:

This reduction in NK cell expansion in response to LPS in patients with type 1 diabetes is consistent with a non-genetically determined alteration in the innate immune response either predisposing to or resulting from the disease. Copyright © 2006 John Wiley & Sons, Ltd.

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