PT  - JOURNAL ARTICLE
AU  - Moujtaba Y Kasmani
AU  - Ashley E Ciecko
AU  - Ashley K Brown
AU  - Galina Petrova
AU  - Jack Gorski
AU  - Yi-Guang Chen
AU  - Weiguo Cui
TI  - Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage
AID  - 10.26508/lsa.202201503
DP  - 2022 Oct 01
TA  - Life Science Alliance
PG  - e202201503
VI  - 5
IP  - 10
4099  - https://www.life-science-alliance.org/content/5/10/e202201503.short
4100  - https://www.life-science-alliance.org/content/5/10/e202201503.full
SO  - Life Sci. Alliance2022 Oct 01; 5
AB  - Type 1 diabetes (T1D) is an autoimmune disorder defined by CD8 T cell–mediated destruction of pancreatic β cells. We have previously shown that diabetogenic CD8 T cells in the islets of non-obese diabetic mice are phenotypically heterogeneous, but clonal heterogeneity remains relatively unexplored. Here, we use paired single-cell RNA and T-cell receptor sequencing (scRNA-seq and scTCR-seq) to characterize autoreactive CD8 T cells from the islets and spleens of non-obese diabetic mice. scTCR-seq demonstrates that CD8 T cells targeting the immunodominant β-cell epitope IGRP206-214 exhibit restricted TCR gene usage. scRNA-seq identifies six clusters of autoreactive CD8 T cells in the islets and six in the spleen, including memory and exhausted cells. Clonal overlap between IGRP206-214–reactive CD8 T cells in the islets and spleen suggests these cells may circulate between the islets and periphery. Finally, we identify correlations between TCR genes and T-cell clonal expansion and effector fate. Collectively, our work demonstrates that IGRP206-214–specific CD8 T cells are phenotypically heterogeneous but clonally restricted, raising the possibility of selectively targeting these TCR structures for therapeutic benefit.