Regulation of EAE by spontaneously generated IL-10-secreting regulatory T cells in HLA-DR15/TCR.Ob1A12 double transgenic mice.

Abstract

Humanized double transgenic mice express both HLA-DR15 (the MHC gene linked to MS) and TCR.Ob1A12 from a multiple sclerosis patient (that recognizes MBP85-99 presented by HLA-DR15), yet they fail to develop autoimmune encephalomyelitis quickly, although 5-10% develop disease at 12months. These mice were found to express large numbers of IL-10-secreting splenocytes as early as 4weeks of age. These regulatory T cells appeared spontaneously without prior immunization with the autoantigen MBP85-99. They were of murine origin and had a cytokine secretion profile and surface phenotype similar to that reported for Tr1 cells. Notably, the frequency of disease appeared to increase at 14months. The diseased mice had small spleens which averaged 47mg, while the remaining non-diseased mice in our colony killed at ages 14-15months had splenocytes that averaged 80mg (ranging from 47-130mg). Thus, the appearance of disease was associated with diminution in numbers of IL-10-secreting regulatory T cells with age.