IL-2-engineered nano-APC effectively activates viral antigen-mediated T cell responses from chronic hepatitis B virus-infected patients.
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.
Division of Bioscience, Brunel University, London UB8 3PH, United Kingdom.
Mengya
M
Liu
Tizong
T
Miao
Haoxiang
H
Zhu
Alistair L J
AL
Symonds
Li
L
Li
Anna
A
Schurich
Mala K
MK
Maini
Jiming
J
Zhang
Patrick T F
PT
Kennedy
Suling
S
Li
Ping
P
Wang
D017951:Antigen Presentation / Q000187:drug effects*; D000956:Antigens, Viral / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects*; D053758:Nanoparticles / Q000627:therapeutic use; D015202:Protein Engineering; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D007376:Interleukin-2