In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 1_Supplement ( 2015-05-01), p. 216.3-216.3
Abstract:
Chronic infection with Hepatitis C Virus (HCV) results in T cell exhaustion and subsequent impairment of T cell immunity. Recently, novel therapies of direct acting antiviral (DAA) regimens were developed which induce rapid and sustained clearance of HCV. These DAAs have provided the unique opportunity to determine whether successful treatment-induced eradication of viral antigen leads to reversal of T cell exhaustion and reconstitution T cell effector function. Herein we found that treatment with DAAs resulted in the reconstitution of the immune compartment in the peripheral blood. Furthermore, DAA-mediated viral clearance induced the re-differentiation of the memory T cell compartment to a more effector like state. Finally, DAA treatment caused the down modulation of markers associated with T cell chronic exhaustion, most intriguingly, the co-inhibitory T cell immunoglobulin and ITIM domain (TIGIT). The down modulation of TIGIT was unique to DAA treatment, as this effect was not observed when patients were treated with standard pegylated IFN and ribavirin therapy. Collectively, our data demonstrates that rapid HCV viral clearance following treatment with DAAs resulted in the partial restoration of global and viral specific T cell immunity. These findings suggest that T cell chronic exhaustion can persist long term in the absence of viral antigen and that complete reversal of this phenotype requires interventions that are independent of the persistence of viral antigen.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.194.Supp.216.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2015
detail.hit.zdb_id:
1475085-5
Permalink
