Identical beta cell-specific CD8(+) T cell clonotypes typically reside in both peripheral blood lymphocyte and pancreatic islets.
A major issue regarding T cell responses in autoimmunity is how the repertoire compares between the periphery and target organ. In type 1 diabetes, the status of at-risk or diabetic individuals can be monitored by measuring beta cell-specific T cells isolated from PBL, but whether these T cells accurately reflect the repertoire residing in the pancreatic islets is unclear. The TCR repertoire of disease-relevant, tetramer-sorted CD8(+) T cells was examined at the single-cell level in PBL, pancreatic lymph nodes (PLN), and the islets of individual NOD mice. CDR3alpha and CDR3beta sequences demonstrated that the same repertoire of T cells in PBL was detected in the islets and PLN, although the frequency of specific clonotypes varied. Albeit infrequent, clonotypes that were prevalent in the islets but not found in PBL were also detected. beta cell Ag immunization expanded immunodominant PBL clonotypes present in the islets and PLN. These results show that insight into repertoire profiles of islet-infiltrating T cells can be obtained from PBL.
Wong
Carmen P
CP
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Stevens
Rosemary
R
Long
Brian
B
Li
Li
L
Wang
Yaming
Y
Wallet
Mark A
MA
Goudy
Kevin S
KS
Frelinger
Jeffrey A
JA
Tisch
Roland
R
D000818:Animals; D015551:Autoimmunity; D001773:Blood Cells / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D002999:Clone Cells / Q000276:immunology; D050417:Insulin-Secreting Cells / Q000276:immunology*; D007515:Islets of Langerhans / Q000166:cytology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D037182:T-Cell Antigen Receptor Specificity