In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 76.6-76.6
Abstract:
Accumulating epidemiological evidence suggests that chronic infections compromise immunity against antigenically unrelated infections, but the underlying mechanisms are unclear. We investigated whether antigenically unrelated “bystander” chronic infections impacted the development of memory CD8 T cells, the hallmarks of protective immunity against intracellular pathogens. We demonstrate that chronic bystander infection and inflammation substantially impair memory CD8 T cell responses in several mouse models with similar changes in non-human primates and in chronically HCV -infected humans. Type I IFN -induced molecular pathways were specifically dysregulated in memory CD8 T cells in inflammatory environments and induction of type I IFN by chronic poly(I:C) administration similarly impaired memory CD8 T cell development and function. Chronic inflammation increased the expression of the proapoptotic protein Bim in bystander CD8 T cells, while inhibiting their IL15-induced rescue from apoptosis ex vivo. Two transcriptional regulators of T cell development, Blimp-1 and T-bet, integrated the effects of inflammatory mediators in impairing optimal memory CD8 T cell development. Thus, exposure to chronic bystander infections deregulates the normal effector to memory CD8 T cell transition. These results have direct relevance concerning current therapeutic approaches and vaccination strategies for patients with persisting infections or chronic inflammatory conditions.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.76.6
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
