Insulin‐specific T cells are a predominant component of islet infiltrates in pre‐diabetic NOD mice

TLDR

T cells play a key role in β‑cell destruction in the NOD mouse, a widely used model of type I diabetes. This study aims to establish and characterize islet‑specific T cell lines from pre‑diabetic NOD mice and to generate a large panel of clones. The authors isolated islet‑infiltrating lymphocytes from individual pre‑diabetic mice, derived multiple T cell lines, and expanded numerous clones from these lines. Insulin‑specific T cells constitute a major component of the spontaneous islet response, with 55 % of clones from 12‑week‑old mice and 14 % from 7‑week‑old mice responding to insulin.

Abstract

Abstract Numerous investigations have demonstrated that T cells are involved in destruction of β cells in the NOD mouse, a widely studied model of type I diabetes. In this report we describe a series of islet‐specific T cell lines established from islet‐infiltrating lymphocytes obtained from individual pre‐diabetic NOD mice as well as a large panel of clones derived from these lines. Proliferation assays indicated that these nominally islet‐specific lines responded vigorously to porcine insulin. Furthermore, of 40 islet‐specific clones derived from lines established from 12‐week‐old mice, 22 (55%) responded to insulin. A similar analysis of islet‐specific clones established from 7‐week‐old mice indicated that 2 of 14 (14%) were insulin specific. These findings demonstrate that insulin‐specific T cells can comprise a major portion of the spontaneously arising T cell response to islets in NOD mice.