Journal of Molecular Medicine

, Volume 87, Issue 12, pp 1173–1178

The primacy of CD8 T lymphocytes in type 1 diabetes and implications for therapies


DOI: 10.1007/s00109-009-0516-6

Cite this article as:
Faustman, D.L. & Davis, M. J Mol Med (2009) 87: 1173. doi:10.1007/s00109-009-0516-6


Type I diabetes (TID) is an autoimmune disease in which insulin-secreting beta cells of the pancreatic islets are destroyed by T lymphocytes. Until the 1990s, the prevailing dogma was that the attack was attributable to rogue T lymphocytes bearing CD4 markers on their surface (CD4 T helper lymphocytes). Today, the prevailing view is that rogue T cells bearing CD8 markers or cytotoxic CD8 T lymphocytes are also important and perhaps the foremost contributors to beta-cell death. Recognizing CD8 T-cell subsets as the prime culprits has helped to trace the disease's pathogenesis to abnormal T-cell education. Defective education can occur when antigen-presenting cells fail to assemble and present self-antigens to naïve T cells. The failure in that process, normally designed to prevent T cells' attack on the body's own antigens, enables self-reactive T cells to escape into the circulation. Once released, the self-reactive CD8 T cells kill specific self-antigens, which, in the case of TID, include insulin and other key proteins associated with beta cell functions. Abnormalities during T-cell education have been mapped in part to genetic defects in specific gene-encoding regions of the major histocompatibility complex class I region and to proteins that assemble self-peptides into the MHC class I structure that map within the MHC class II region. Two decades of research have led to understanding of genetic and functional defects in the immune system, placing us at the threshold of finding new therapeutic strategies aimed at eliminating autoreactive CD8 T cells, while preserving healthy immune cells.


Autoimmunity Immune tolerance Type 1 diabetes MHC class I Proteasome T cell 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Immunobiology LaboratoryMassachusetts General Hospital and Harvard Medical SchoolCharlestownUSA

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