The Clinical Significance of Hepatic CD69 CD103 CD8 Resident-Memory T Cells in Autoimmune Hepatitis.

Background And Aims: The diverse inflammatory response found in the liver of patients with autoimmune hepatitis (AIH) is well established, but identification of potentially pathogenic subpopulations has proven enigmatic.

Approach And Results: We report herein that CD69 CD103 CD8 tissue-resident memory T cells (T ) are significantly increased in the liver of patients with AIH compared to chronic hepatitis B, NAFLD, and healthy control tissues. In addition, there was a significant statistical correlation between elevation of CD8 T cells and AIH disease severity. Indeed, in patients with successful responses to immunosuppression, the frequencies of such hepatic CD8 T cells decreased significantly. CD69 CD8 and CD69 CD103 CD8 T cells, also known as CD8 T cells, reflect tissue residency and are well known to provide intense immune antigenic responses. Hence, it was particularly interesting that patients with AIH also manifest an elevated expression of IL-15 and TGF-β on inflammatory cells, and extensive hepatic expression of E-cadherin; these factors likely contribute to the development and localization of CD8 T cells. Based on these data and, in particular, the relationships between disease severity and CD8 T cells, we studied the mechanisms involved with glucocorticoid (GC) modulation of CD8 T cell expansion. Our data reflect that GCs in vitro inhibit the expansion of CD8 T cells induced by IL-15 and TGF-β and with direct down-regulation of the nuclear factor Blimp1 of CD8 T cells.

Conclusions: Our data suggest that CD8 T cells play a critical role in the pathogenesis of AIH, and GCs attenuate hepatic inflammation through direct inhibition of CD8 T cell expansion.