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

Abstract 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.