| Autor: |
DiLorenzo TP; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Graser RT, Ono T, Christianson GJ, Chapman HD, Roopenian DC, Nathenson SG, Serreze DV |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 1998 Oct 13; Vol. 95 (21), pp. 12538-43. |
| DOI: |
10.1073/pnas.95.21.12538 |
| Abstrakt: |
Nonobese diabetic (NOD) mice develop insulin-dependent diabetes mellitus due to autoimmune T lymphocyte-mediated destruction of pancreatic beta cells. Although both major histocompatibility complex class I-restricted CD8(+) and class II-restricted CD4(+) T cell subsets are required, the specific role each subset plays in the pathogenic process is still unclear. Here we show that class I-dependent T cells are required for all but the terminal stages of autoimmune diabetes development. To characterize the diabetogenic CD8(+) T cells responsible, we isolated and propagated in vitro CD8(+) T cells from the earliest insulitic lesions of NOD mice. They were cytotoxic to NOD islet cells, restricted to H-2Kd, and showed a diverse T cell receptor beta chain repertoire. In contrast, their alpha chain repertoire was more restricted, with a recurrent amino acid sequence motif in the complementarity-determining region 3 loop and a prevalence of Valpha17 family members frequently joined to the Jalpha42 gene segment. These results suggest that a number of the CD8(+) T cells participating in the initial phase of autoimmune beta cell destruction recognize a common structural component of Kd/peptide complexes on pancreatic beta cells, possibly a single peptide. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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