| First Author | Oldstone MB | Year | 2012 |
| Journal | PLoS Pathog | Volume | 8 |
| Issue | 11 | Pages | e1003044 |
| PubMed ID | 23209415 | Mgi Jnum | J:195572 |
| Mgi Id | MGI:5484819 | Doi | 10.1371/journal.ppat.1003044 |
| Citation | Oldstone MB, et al. (2012) Molecular anatomy and number of antigen specific CD8 T cells required to cause type 1 diabetes. PLoS Pathog 8(11):e1003044 |
| abstractText | We quantified CD8 T cells needed to cause type 1 diabetes and studied the anatomy of the CD8 T cell/beta (beta) cell interaction at the immunologic synapse. We used a transgenic model, in situ tetramer staining to distinguish antigen specific CD8 T cells from total T cells infiltrating islets and a variety of viral mutants selected for functional deletion(s) of various CD8 T cell epitopes. Twenty percent of CD8 T cells in the spleen were specific for all immunodominant and subdominant viral glycoprotein (GP) epitopes. CTLs to the immunodominant LCMV GP33-41 epitope accounted for 63% of the total (12.5% of tetramers). In situ hybridization analysis demonstrated only 1 to 2% of total infiltrating CD8 T cells were specific for GP33 CD8 T cell epitope, yet diabetes occurred in 94% of mice. The immunologic synapse between GP33 CD8 CTL and beta cell contained LFA-1 and perforin. Silencing both immunodominant epitopes (GP33, GP276-286) in the infecting virus led to a four-fold reduction in viral specific CD8 CTL responses, negligible lymphocyte infiltration into islets and absence of diabetes. |
