Activated T cell subsets in human type 1 diabetes: evidence for expansion of the DR+ CD30+ subpopulation in new-onset disease

C Baker, L Chang, K A Elsegood, A J Bishop, D H Gannon, P Narendran, N J Leech, C M Dayan

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)

Abstract

An important limitation in T cell studies of human autoimmune (type 1) diabetes is lack of direct access to cells infiltrating the pancreas. We hypothesized that cells recently released from the pancreas into the blood might express a characteristic combination of markers of activation. We therefore examined the recently activated circulating T cell population [CD3+, human leucocyte antigen D-related (HLA-DR+)] using cytokine production and 10 additional subset markers [CD69, CD25, CD122, CD30, CD44v6, CD57, CD71, CCR3 (CD193), CCR5 (CD195) or CXCR3 (CD183)], comparing newly diagnosed adult (ND) (age 18-40 years) patients (n=19) to patients with diabetes for >10 years [long-standing (LS), n=19] and HLA-matched controls (C, n=16). CD3+ DR+ cells were enriched by two-step immunomagnetic separation. No differences in basal or stimulated production of interleukin (IL)-4, IL-10, IL-13 or interferon (IFN)-gamma by CD3+ DR+ enriched cells were observed between the different groups of subjects. However, among the CD3+ DR+ population, significant expansions appeared to be present in the very small CD30+, CD69+ and CD122+ subpopulations. A confirmatory study was then performed using new subjects (ND=26, LS=15), three-colour flow cytometry, unseparated cells and three additional subset markers (CD38, CD134, CD4/CD25). This confirmed the expansion of the CD3+ DR+ CD30+ subpopulation in ND subjects. We conclude that a relative expansion in the T cell subpopulation with the activated phenotype CD3+ DR+ CD30+ is seen in the peripheral blood of subjects with newly diagnosed type 1 diabetes. This subpopulation represents less than 0 x 7% of circulating T cells and may provide a rich source of disease-specific T cells that can be isolated from blood.

Original languageEnglish
Pages (from-to)472 - 482
Number of pages11
JournalClinical and Experimental Immunology
Volume147
Issue number3
DOIs
Publication statusPublished - Mar 2007

Bibliographical note

Publisher: Blackwell

Keywords

  • Adolescent
  • Adult
  • Antigens, CD3
  • Antigens, CD30
  • Cytokines
  • Diabetes Mellitus, Type 1
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HLA-DR Antigens
  • Histocompatibility Testing
  • Humans
  • Immunomagnetic Separation
  • Lymphocyte Activation
  • Male
  • T-Lymphocyte Subsets
  • Time Factors

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