Distinct Effector Programs of Brain-Homing CD8 + T Cells in Multiple Sclerosis.

Autor: Koetzier, Steven C., van Langelaar, Jamie, Melief, Marie-José, Wierenga-Wolf, Annet F., Corsten, Cato E. A., Blok, Katelijn M., Hoeks, Cindy, Broux, Bieke, Wokke, Beatrijs, van Luijn, Marvin M., Smolders, Joost
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Zdroj: Cells (2073-4409); May2022, Vol. 11 Issue 10, p1634-N.PAG, 12p
Abstrakt: The effector programs of CD8+ memory T cells are influenced by the transcription factors RUNX3, EOMES and T-bet. How these factors define brain-homing CD8+ memory T cells in multiple sclerosis (MS) remains unknown. To address this, we analyzed blood, CSF and brain tissues from MS patients for the impact of differential RUNX3, EOMES and T-bet expression on CD8+ T cell effector phenotypes. The frequencies of RUNX3- and EOMES-, but not T-bet-expressing CD8+ memory T cells were reduced in the blood of treatment-naïve MS patients as compared to healthy controls. Such reductions were not seen in MS patients treated with natalizumab (anti-VLA-4 Ab). We found an additional loss of T-bet in RUNX3-expressing cells, which was associated with the presence of MS risk SNP rs6672420 (RUNX3). RUNX3+EOMES+T-bet− CD8+ memory T cells were enriched for the brain residency-associated markers CCR5, granzyme K, CD20 and CD69 and selectively dominated the MS CSF. In MS brain tissues, T-bet coexpression was recovered in CD20dim and CD69+ CD8+ T cells, and was accompanied by increased coproduction of granzyme K and B. These results indicate that coexpression of RUNX3 and EOMES, but not T-bet, defines CD8+ memory T cells with a pre-existing brain residency-associated phenotype such that they are prone to enter the CNS in MS. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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