It has been well-established that some of the residual insulin-containing islets found in T1D patients exhibit hyperexpression of MHC class I. Evidence indicates that this overexpression may be driven through production of interferons by stressed β cells and by infiltrating activated immune cells and their release of inflammatory cytokines. There is also increasing evidence of a viral signature in residual islets of T1D patients. Given that overexpression of MHC class I occurs following viral infections, the following question arises:
Is MHC class I overexpression on residual islets associated with a viral signature? If yes, what are the defects associated in T1D patients that fail to clear certain viral infections, thus, leading to this hyperexpression? Is it related to a defect in natural killer cells, our first line of defense against viral infections? Are these questions more suited to be addressed in the NOD mouse model where a stepwise approach could address these questions? Or finally, is this question better addressed by examining at-risk and T1D patient samples, perhaps as a longitudinal study looking for viral, natural killer, and interferon signatures and studying their relationships?
thought experiment proposed by Allison Bayer, PhD, UMiami