# Establishment of Autoreactive CD4+CD8+ T Cell Hybridomas from Sjögren’s Disease Model, SATB1 Conditional Knockout Mice

## TL;DR

Researchers found that abnormal CD4+CD8+ T cells in SATB1 knockout mice may contribute to the autoimmune disease Sjögren’s syndrome.

## Contribution

Establishment of autoreactive CD4+CD8+ T cell hybridomas from SATB1 conditional knockout mice to study Sjögren’s disease pathogenesis.

## Key findings

- CD4+CD8+ T cells were more frequent in salivary glands than spleen in SATB1cKO mice.
- Five out of six hybridoma clones showed fetal or immature TCRβ gene characteristics.
- Four clones upregulated IL-2 transcription in T/B cell-deficient mice, indicating autoreactivity.

## Abstract

Sjögren’s disease (SjD), which is also known as Sjögren’s syndrome (SS), is a chronic autoimmune disease characterized by dysfunction of exocrine glands, such as the salivary and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). Mice in which the SATB1 gene is conditionally deleted in hematopoietic cells (SATB1cKO mice) develop SS as early as 4 weeks of age; however, the etiology of the disease remains to be elucidated. Here, we found that the frequency of abnormally appearing CD4+CD8+ double positive (DP) T cells in the periphery of SATB1cKO mice was higher in the salivary glands than that in the spleen, suggesting a possible involvement of DP T cells in the pathogenesis of SS in SATB1cKO mice. To investigate the nature of DP T cells, we established DP T cell hybridomas by fusing T cells from the cervical lymph nodes of SATB1cKO mice with the BW5147 thymoma cell line. Among six DP hybridoma clones, the TCRβ gene from five clones exhibited a fetal or immature phenotype. In addition, four out of five clones exhibited upregulated transcription of IL-2 in the salivary glands of T/B cell-deficient RAG2−/− mice, suggesting that autoreactive T cells were enriched in the DP T cell population of SATB1cKO mice. These results suggest that unusual DP T cells in SATB1cKO mice may be involved in autoimmune pathogenesis in SATB1cKO mice.