Journal
JOURNAL OF IMMUNOLOGY
Volume 188, Issue 3, Pages 1534-1543Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1102709
Keywords
-
Categories
Funding
- Medical Research Council
- Interactive China UK Fund
- Science and Technology Commission of Shanghai Municipality, China
- MRC [G0801213, G0300520] Funding Source: UKRI
- Medical Research Council [G0300520, G0801213] Funding Source: researchfish
Ask authors/readers for more resources
Impaired function of virus-specific T cells resulting from virus persistence is one of the major mechanisms underlying the development of chronic hepatitis B viral infection. Previously, we found that IL-2 can restore the effector function of T cells rendered tolerant by Ag persistence. However, systemic administration of IL-2 induces organ pathology and expansion of T regulatory cells. In this study, we show that nano-APC with engineered HLA alleles and IL-2 deliver peptide-MHC complexes, costimulatory molecules, and IL-2 to Ag-responding T cells, resulting in enhanced expression of CD25 and activation of TCR signaling pathways, while suppressing PD-1 expression on viral-responding CD8 T cells from chronic hepatitis B virus patients. The enhanced activation of CD4 and CD8 T cells induced by IL-2-nano-APC was Ag dependent and IL-2-nano-APC did not affect T regulatory cells. At a size of 500 nm, the nano-APC effectively induce immune synapse formation on Ag-specific T cells and accumulate as free particles in the lymphoid organs. These attributes of IL-2-nano-APC or other bioadjuvant-engineered nano-APC have profound implications for their use as a therapeutic strategy in the treatment of chronic hepatitis B virus infection or other chronic viral diseases. The Journal of Immunology, 2012, 188: 1534-1543.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available