In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 129.6-129.6
Abstract:
PD-1 is highly expressed on CD8 T cells during activation, both in acute and chronic viral infections. Inhibitory signaling in cytotoxic T cells through the PD-1 axis is well characterized during chronic infections and has led to the development of potent blockade therapies that restore function to otherwise exhausted CD8 T cells. However, the functional significance of transiently increased PD-1 expression on CD8 T cells early after activation and its rapid down-regulation following clearance of antigen during acute infections, remains to be characterized. The enigma is – expression of PD-1 (an immunological brake) during activation temporally coincides with rapid proliferation and production of copious amounts of signature effector cytokines (IFN-γ and TNF-α). We generated PD-1−/− antigen-specific CD8 T cells to study its cell-intrinsic role during acute infection with LCMV. Unexpectedly, PD-1−/− cells did not exhibit increased proliferation early during infection, or enhanced accumulation at the peak of expansion. PD-1−/− CD8 T cells were also unaltered in their polyfunctionality and granzyme B expression. Despite robust effector properties, PD-1−/− CD8 T cells underwent precipitous contraction, leading to near ablation of the memory pool. Mechanistically, in vivo analysis of PD-1−/− memory cells showed a severe defect in antigen-independent homeostatic proliferation due to decreased sensitivity to IL-2, −7, and −15 signals, without evident change in the expression of common gamma-chain cytokine receptors. These studies demonstrate a previously unrecognized role of PD-1 signaling in programming of memory CD8 T cell maintenance and could make it a novel target for manipulating vaccine-induced memory T cell longevity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.129.6
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
