RESUMO
We previously reported a significant increase in percentages of peripheral blood gamma delta+ T cells in islet cell antibody (ICA) positive relatives of patients with insulin-dependent diabetes (IDD). In the present study, we further characterized this T cell abnormality in a larger group of ICA+ subjects and report that (1) Percentages of gamma delta+ T lymphocytes were significantly increased only in subjects with high ICA titers (> or = 20 JDF units) (P = 0.005) and resulted from an increase in absolute numbers of gamma delta+ T lymphocytes. (2) In these subjects, the increase in gamma delta+ T lymphocytes was associated with an increase in the V gamma 9 V delta 2 subpopulation (r = 0.99). (3) In these same subjects, high percentages of gamma delta+ T lymphocytes were associated with normal beta cell function while low percentages were associated with diminished insulin response. Using 65 microU/ml as the threshold of abnormal intravenous glucose tolerance test (IVGTT) response, percentages of gamma delta+ T lymphocytes could significantly predict IVGTT status in these subjects (P < 0.01). A longitudinal follow-up further suggested that the development of an abnormal IVGTT response and progression to diabetes was associated with a decrease in percentages of gamma delta+ T lymphocytes while patients whose gamma delta+ T cell percentages remained high retained normal beta cell function. Our data therefore suggest that gamma delta+ T lymphocytes and more specifically V gamma 9 V delta 2 T cells are implicated in the autoimmune process leading to diabetes and may have a regulatory role. The monitoring of their percentages in the blood of patients at risk for diabetes may be useful as an additional predictor of diabetes development.
Assuntos
Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/análise , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Teste de Tolerância a Glucose , Humanos , Imunidade Celular , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/fisiopatologia , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/patologia , Fatores de TempoRESUMO
The effector mechanisms responsible for autoimmune beta cell destruction in insulin dependent (type 1) diabetes (IDD) remain elusive. In order to investigate whether T lymphocytes bearing the gamma-delta T cell receptor (gamma delta+ T cells) could be involved in this process, we measured percentages of peripheral blood gamma delta+ T cells in IDD patients, relatives of IDD probands and controls. High levels of gamma delta+ T cells strongly differentiated 23 relatives at high risk for IDD on the basis of positive islet cell autoantibodies (ICA positive relatives) from 59 controls (P = 0.0013), whereas 26 ICA negative relatives, 14 recent-onset and nine long term IDD patients could not be distinguished from controls on the basis of percentages of gamma delta+ T cells. These data suggest that increased levels of circulating gamma delta+ T cells correlate with the ongoing autoimmune process in pancreatic islets of subjects at high risk for IDD and may thus represent an additional marker for the development of the disease.