Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 2 of 2

Publication Record

Connections

Viral acute lower respiratory infections impair CD8+ T cells through PD-1.
Erickson JJ, Gilchuk P, Hastings AK, Tollefson SJ, Johnson M, Downing MB, Boyd KL, Johnson JE, Kim AS, Joyce S, Williams JV
(2012) J Clin Invest 122: 2967-82
MeSH Terms: Acute Disease, Animals, Antigens, Viral, CD8-Positive T-Lymphocytes, HLA-B7 Antigen, Humans, Imidazoles, Immunologic Memory, Influenza A Virus, H1N1 Subtype, Influenza, Human, Lung, Metapneumovirus, Mice, Mice, Transgenic, Paramyxoviridae Infections, Programmed Cell Death 1 Receptor, Pyridines, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Respiratory Tract Infections, Signal Transduction, Up-Regulation, Virus Diseases
Show Abstract · Added March 20, 2014
Viruses are leading causes of severe acute lower respiratory infections (LRIs). These infections evoke incomplete immunity, as individuals can be repeatedly reinfected throughout life. We report that acute viral LRI causes rapid pulmonary CD8+ cytotoxic T lymphocyte (TCD8) functional impairment via programmed death-1/programmed death ligand-1 (PD-1/PD-L1) signaling, a pathway previously associated with prolonged antigenic stimulation during chronic infections and cancer. PD-1-mediated TCD8 impairment occurred acutely in mice following infection with human metapneumovirus or influenza virus. Viral antigen was sufficient for PD-1 upregulation, but induction of PD-L1 was required for impairment. During secondary viral infection or epitope-only challenge, memory TCD8 rapidly reexpressed PD-1 and exhibited severe functional impairment. Inhibition of PD-1 signaling using monoclonal antibody blockade prevented TCD8 impairment, reduced viral titers during primary infection, and enhanced protection of immunized mice against challenge infection. Additionally, PD-1 and PD-L1 were upregulated in the lungs of patients with 2009 H1N1 influenza virus, respiratory syncytial virus, or parainfluenza virus infection. These results indicate that PD-1 mediates TCD8 functional impairment during acute viral infection and may contribute to recurrent viral LRIs. Therefore, the PD-1/PD-L1 pathway may represent a therapeutic target in the treatment of respiratory viruses.
1 Communities
3 Members
0 Resources
23 MeSH Terms
Identification of potential human respiratory syncytial virus and metapneumovirus T cell epitopes using computational prediction and MHC binding assays.
Rock MT, McKinney BA, Yoder SM, Prudom CE, Wright DW, Crowe JE
(2011) J Immunol Methods 374: 13-7
MeSH Terms: Algorithms, Antigens, Viral, Epitope Mapping, Epitopes, T-Lymphocyte, HLA Antigens, HLA-A1 Antigen, HLA-A2 Antigen, HLA-B7 Antigen, Humans, Metapneumovirus, Peptide Fragments, Respiratory Syncytial Virus, Human
Show Abstract · Added August 6, 2012
Human respiratory syncytial virus (RSV) and human metapneumovirus (MPV) are two of the most common causes of serious viral lower respiratory tract illness in humans. CD8+ T cells have been shown to be important in animal models and human clinical studies for the clearance of viral infection, and they may contribute in part to protection against severe disease during reinfections. Precise enumeration and accurate phenotyping of RSV- or MPV-specific CD8+ T cells in humans is currently limited by the relatively small number of T cell epitopes that have been mapped with accompanying identification of MHC restriction patterns. We sought to expand the number of potential RSV and MPV epitopes for use in clinical and translational studies by identifying an expanded set of MHC-binding peptides based on RSV and MPV wild-type virus strain protein sequences. We interrogated the full protein sequences of all 9 or 11 proteins of MPV or RSV respectively using four established epitope prediction algorithms for human HLA A*0101, A*0201, or B*0702 binding and attempted to synthesize the top-scoring 150-152 peptides for each of the two viruses. Synthesis resulted in 442 synthesized and soluble peptides of the 452 predicted epitopes for MPV or RSV. We then determined the binding of the synthetic peptides to recombinant human HLA A*0101, A*0201 or B*0702 molecules with the predicted restriction using a commercially available plate-based assay, iTopia. A total of 230 of the 442 peptides tested exhibited binding to the appropriate MHC molecule. The binding results suggested that existing algorithms for prediction of MHC A*0201 binding are particularly robust. The binding results also provided a large benchmarking data collection for comparison of new prediction algorithms.
Copyright © 2011 Elsevier B.V. All rights reserved.
0 Communities
1 Members
0 Resources
12 MeSH Terms