Visualization and Characterization of Respiratory Syncytial Virus F-Specific CD8+ T Cells During Experimental Virus Infection

• Published in: The Journal of immunology (1950) 2001-10, Vol.167 (8), p.4254-4260
• Main Authors: Chang, Jun, Srikiatkhachorn, Anon, Braciale, Thomas J
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Viral - immunology; Epitope Mapping; Female; H-2 Antigens - immunology; Immunodominant Epitopes - immunology; Lung - cytology; Lung - immunology; Mice; Peptide Fragments - immunology; Respiratory Syncytial Virus Infections - immunology; Spleen - cytology; Spleen - immunology; T-Lymphocytes, Cytotoxic - immunology; Viral Proteins - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.8.4254

CTL play a major role in the clearance of respiratory syncytial virus (RSV) during experimental pulmonary infection. The fusion (F) glycoprotein of RSV is a protective Ag that elicits CTL and Ab response against RSV infection in BALB/c mice. We used the strategy of screening a panel of overlapping synthetic peptides corresponding to the RSV F protein and identified an immunodominant H-2K(d)-restricted epitope (F(85-93); KYKNAVTEL) recognized by CD8(+) T cells from BALB/c mice. We enumerated the F-specific CD8(+) T cell response in the lungs of infected mice by flow cytometry using tetramer staining and intracellular cytokine synthesis. During primary infection, F(85-93)-specific effector CD8(+) T cells constitute approximately 4.8% of pulmonary CD8(+) T cells at the peak of the primary response (day 8), whereas matrix 2-specific CD8(+) T cells constituted approximately 50% of the responding CD8(+) T cell population in the lungs. When RSV F-immune mice undergo a challenge RSV infection, the F-specific CD8(+) T cell response is accelerated and dominates, whereas the primary response to the matrix 2 epitope in the lungs is reduced by approximately 20-fold. In addition, we found that activated F-specific effector CD8(+) T cells isolated from the lungs of RSV-infected mice exhibited a lower than expected frequency of IFN-gamma-producing CD8(+) T cells and were significantly impaired in ex vivo cytolytic activity compared with competent F-specific effector CD8(+) T cells generated in vitro. The significance of these results for the regulation of the CD8(+) T cell response to RSV is discussed.