CD43 regulates T-cell function and survival in a context-dependent manner 2299796

Abstract

Abstract Introduction CD43 (sialophorin) is a sialomucin widely expressed on hematopoietic cells that governs T-cell adhesion, trafficking, and activation. We tested whether CD43 sets proliferation and survival thresholds in T-cell subsets. Methods Lymph-node T cells from WT and CD43KO C57BL/6 mice were stimulated with anti-CD3/CD28 or PMA/ionomycin; proliferation (CFSE), viability, Bax/Bcl-xL, and GLUT1, CD25, and CD69 were quantified by flow cytometry. For antigen-specific responses, CFSE-labeled OT-I/OT-II WT or CD43KO T cells were adoptively transferred into OVA-immunized recipients. Results Under anti-CD3/CD28, CD43KO CD4 and CD8 proliferated less than WT, indicating that CD43 supports TCR/CD28-driven activation. With PMA/ionomycin, CD43KO CD4 proliferated less, whereas CD43KO CD8 proliferated more. Loss of CD43 pushed CD4 toward a pro-apoptotic, hypoproliferative state characterized by an increased Bax/Bcl-xL ratio, while CD43KO CD8 retained a balanced Bax/Bcl-xL and showed more GLUT1+ and CD69+ cells, consistent with elevated metabolic/activation thresholds. CD25 was unchanged. In vivo, OT-I CD43KO cells expanded 5-fold over WT, whereas OT-II CD43KO cells expanded 4-fold less than WT. Conclusion CD43 has a context-dependent, subset-specific role in T-cell responses differentially tuning CD4+ and CD8+ activation and expansion. CD4+ cells are more prone to activation-induced death and require CD43 for proper expansion, whereas CD8+ cells are restrained by CD43, limiting excessive activation. Thus, CD43 shapes the magnitude and quality of T-cell immunity across contexts. Funding Source Funded by DGAPA/UNAM IN222523, Postdoctoral fellow by SECIHTI, 6002103. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)