Aged Regulatory T Cells Fail to Control Autoimmune Lacrimal Gland Pathogenic CD4+ T Cells

Authors

Kaitlin K Scholand
Laura Schaefer
Gowthaman Govindarajan
Zhiyuan Yu
Jeremias G Galletti
Cintia S de Paiva

Language

English

Publication Date

6-1-2025

Journal

GeroScience

DOI

10.1007/s11357-025-01576-y

PMID

40053297

PMCID

PMC12181515

PubMedCentral® Posted Date

3-7-2025

PubMedCentral® Full Text Version

Post-print

Abstract

CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4+ T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and decreased protein levels of IL-12p40 and VEGF-A. Co-adoptive transfer of CD25KO CD4+ T cells with either young or aged B6 Tregs was performed in RAG1KO mice. Recipients of CD25KO CD4+ T cells alone had higher LG inflammation than naive mice. However, in recipients of young B6 Tregs plus CD25KO CD4+ T cells, LGs had significantly reduced inflammation. Recipients of CD25KO CD4+ T cells with aged B6 Tregs had more inflamed LGs than young Tregs, suggesting aged Tregs have less suppressive capacity in vivo. Altogether, CD25KO mice have phenotypic and genetic changes resulting in increased inflammation and severe lymphocytic infiltration in the LGs. However, this autoimmunity can be controlled by the addition of young, but not aged, Tregs, suggesting that aging Tregs have dysfunctional suppression.

Keywords

Animals, Mice, T-Lymphocytes, Regulatory, Mice, Knockout, Lacrimal Apparatus, Disease Models, Animal, CD4-Positive T-Lymphocytes, Sjogren's Syndrome, Interleukin-2 Receptor alpha Subunit, Mice, Inbred C57BL, Female, Autoimmunity, Sjögren disease, Lacrimal gland, MHC II presentation, Aging, Regulatory T cells

Published Open-Access

yes

Recommended Citation

Scholand, Kaitlin K; Schaefer, Laura; Govindarajan, Gowthaman; et al., "Aged Regulatory T Cells Fail to Control Autoimmune Lacrimal Gland Pathogenic CD4+ T Cells" (2025). Faculty and Staff Publications. 4841.
https://digitalcommons.library.tmc.edu/baylor_docs/4841