T cells co-expressing high levels of CD29 and CD99 show increased cytotoxic potential and are upregulated in Sjögren’s disease

This study aimed to investigate the role of CD29 and CD99 in human T lymphocytes and elucidate its significance in Sjögren's disease (SjD). ScRNA-Seq data were utilized to analyze CD29 and CD99 expression in PBMCs. CD29 and CD99-expressing T lymphocyte proportions in SjD patients and healthy controls were determined by flow cytometry. Bulk RNA-Seq was performed to identify differential gene expression between the CD29hiCD99hi and CD29intCD99int subsets. The roles of CD29 and CD99 were elucidated through the stimulation of T lymphocytes with anti-CD29 and anti-CD99. CD29 and CD99-related subsets were analyzed in SjD patients, and their clinical value was determined using ROC curves. ScRNA-Seq data uncovered a strong positive correlation between CD29 and CD99 in both CD4+ and CD8+ T cells. Flow cytometry confirmed their co-expression, categorizing T cells into CD29intCD99int and CD29hiCD99hi groups. CD29hiCD99hi T cells exhibited high expression of cytotoxic molecules, and displayed activation features, with higher levels of Ki-67, PD-1, and CD25. Stimulation with anti-CD99 and anti-CD29 increased granzyme B levels in CD29hiCD99hi CD8+ T cells. CD29hiCD99hi CD8+ T cells were significantly elevated in SjD. However, ROC analysis indicated that only TIGIT expression in CD29hiCD99hiCD4+ T cells achieved a high AUC value. In conclusion, CD29 and CD99 exhibited significant co-expression in peripheral T cells, while CD29hiCD99hi T cells exhibit increased expression of molecules associated with cytotoxicity and an activated phenotype. The alterations in CD29hiCD99hi T cell subsets among SjD patients may contribute to the early identification of SjD and warrant further longitudinal investigation.