Multiple differences in gene expression in regulatory V alpha 24J alpha Q T cells from identical twins discordant for type 1 diabetes

Quantitative and qualitative defects in CD1d-restricted T cells have been d emonstrated in human and murine autoimmune diseases. To investigate the tra nscriptional consequences of T cell receptor activation in human V alpha 24 J alpha Q T cell clones, DNA microarrays were used to quantitate changes in mRNA levels after anti-CD3 stimulation of clones derived from identical tw ins discordant for type 1 diabetes and IL-4 secretion. Activation resulted in significant modulation of 226 transcripts in the IL-4 secreting clone an d 86 in the IL-4-null clone. Only 28 of these genes were in common. The dif ferences observed suggest both ineffective differentiation of diabetic V al pha 24J alpha Q T cells and a role for invariant T cells in the recruitment and activation of cells from the myeloid lineage.