IMMUNOLOGY DAP12, Naïve T Cells, and the Brain

Abstract:

DAP12 is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing transmembrane protein that appears important for NK cell activation. Bakker et al. created DAP12-deficient mice and observed that although the knockout mice had normal levels of splenic NK cells, the expression of some DAP12-associated proteins (Ly49D and Ly49H) was markedly reduced. Similarly, the ability of DAP12^-/--derived NK cells to lyse certain target cells was also reduced. DAP12^-/- mice treated to develop T cell-dependent experimental autoimmune encephalomyelitis (EAE, a mouse model disease similar to human multiple sclerosis) largely resisted the development of EAE. Those mutant mice that did develop EAE displayed milder symptoms, delayed onset, and spontaneous remission. Additionally, DAP12^-/- T cells were unable to produce interferon-, suggesting that DAP12^-/- T cells are not properly primed. Results from Tomasello et al., who created mice expressing nonfunctional DAP12 mutant proteins, indicated that DAP12-defective dendritic cells (DCs), a subset of antigen-presenting cells that can prime naïve T cells, accumulate in skin and lympho-epithelial tissue. If DAP12-defective DCs are unable to prime T cells, this might explain why DAP12^-/- mice are resistant to induced EAE.

Bakker, A.B.H., Hoek, R.M., Cerwenka, A., Blom, B., Lucian, L., McNeil, T., Murray, R., Phillips, J.H., Sedgwick, J.D., and Lanier, L.L. (2000) DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity 13: 345-353. [Online Journal]

Tomasello, E., Desmoulins, P.-O., Chemin, K., Guia, S., Cremer, H., Ortaldo, J., Love, P., Kaiserlian, D., and Vivier, E. (2000) Combined natural killer cell and dendritic cell functional deficiency in KARAP/DAP12 loss-of-function mutant mice. Immunity 13: 355-364. [Online Journal]